JP2010505958A - 神経防護作用組成物および方法 - Google Patents
神経防護作用組成物および方法 Download PDFInfo
- Publication number
- JP2010505958A JP2010505958A JP2009532414A JP2009532414A JP2010505958A JP 2010505958 A JP2010505958 A JP 2010505958A JP 2009532414 A JP2009532414 A JP 2009532414A JP 2009532414 A JP2009532414 A JP 2009532414A JP 2010505958 A JP2010505958 A JP 2010505958A
- Authority
- JP
- Japan
- Prior art keywords
- composition
- compound
- acid
- group
- nrf2
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 152
- 230000000324 neuroprotective effect Effects 0.000 title claims abstract description 107
- 238000000034 method Methods 0.000 title claims abstract description 66
- 150000001875 compounds Chemical class 0.000 claims abstract description 256
- 102100031701 Nuclear factor erythroid 2-related factor 2 Human genes 0.000 claims abstract description 121
- 101000588302 Homo sapiens Nuclear factor erythroid 2-related factor 2 Proteins 0.000 claims abstract description 120
- 210000002569 neuron Anatomy 0.000 claims abstract description 115
- 101150116862 KEAP1 gene Proteins 0.000 claims abstract description 112
- 239000000651 prodrug Substances 0.000 claims abstract description 57
- 229940002612 prodrug Drugs 0.000 claims abstract description 57
- 238000010494 dissociation reaction Methods 0.000 claims abstract description 14
- 230000005593 dissociations Effects 0.000 claims abstract description 14
- 210000004027 cell Anatomy 0.000 claims description 161
- -1 X 22 Chemical compound 0.000 claims description 134
- 210000004556 brain Anatomy 0.000 claims description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 59
- 150000003839 salts Chemical class 0.000 claims description 57
- 239000000126 substance Substances 0.000 claims description 48
- 102000004190 Enzymes Human genes 0.000 claims description 44
- 108090000790 Enzymes Proteins 0.000 claims description 44
- 125000000217 alkyl group Chemical group 0.000 claims description 43
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 239000003814 drug Substances 0.000 claims description 40
- 229940079593 drug Drugs 0.000 claims description 35
- 230000036542 oxidative stress Effects 0.000 claims description 35
- 208000002193 Pain Diseases 0.000 claims description 33
- 239000002904 solvent Substances 0.000 claims description 30
- 229910052799 carbon Inorganic materials 0.000 claims description 29
- 208000035475 disorder Diseases 0.000 claims description 28
- 150000002148 esters Chemical class 0.000 claims description 28
- 125000003118 aryl group Chemical group 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 26
- BGNXCDMCOKJUMV-UHFFFAOYSA-N Tert-Butylhydroquinone Chemical compound CC(C)(C)C1=CC(O)=CC=C1O BGNXCDMCOKJUMV-UHFFFAOYSA-N 0.000 claims description 26
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 25
- 230000014509 gene expression Effects 0.000 claims description 25
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 208000024891 symptom Diseases 0.000 claims description 24
- 239000004250 tert-Butylhydroquinone Substances 0.000 claims description 24
- 235000019281 tert-butylhydroquinone Nutrition 0.000 claims description 24
- 230000001965 increasing effect Effects 0.000 claims description 23
- 239000002253 acid Substances 0.000 claims description 22
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 22
- VFLDPWHFBUODDF-FCXRPNKRSA-N curcumin Chemical compound C1=C(O)C(OC)=CC(\C=C\C(=O)CC(=O)\C=C\C=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-FCXRPNKRSA-N 0.000 claims description 22
- 208000012902 Nervous system disease Diseases 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
- 125000003342 alkenyl group Chemical group 0.000 claims description 19
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 19
- 238000001727 in vivo Methods 0.000 claims description 19
- 210000001130 astrocyte Anatomy 0.000 claims description 18
- 208000014674 injury Diseases 0.000 claims description 18
- 230000036407 pain Effects 0.000 claims description 18
- 125000003396 thiol group Chemical group [H]S* 0.000 claims description 18
- FJKROLUGYXJWQN-UHFFFAOYSA-N 4-hydroxybenzoic acid Chemical compound OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 claims description 17
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 16
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 16
- XNGIFLGASWRNHJ-UHFFFAOYSA-N phthalic acid Chemical compound OC(=O)C1=CC=CC=C1C(O)=O XNGIFLGASWRNHJ-UHFFFAOYSA-N 0.000 claims description 16
- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 15
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 239000012453 solvate Substances 0.000 claims description 15
- 241000124008 Mammalia Species 0.000 claims description 14
- ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical compound OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 claims description 14
- 238000000338 in vitro Methods 0.000 claims description 14
- 206010012289 Dementia Diseases 0.000 claims description 12
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 12
- 208000019901 Anxiety disease Diseases 0.000 claims description 11
- 230000030833 cell death Effects 0.000 claims description 11
- 235000012754 curcumin Nutrition 0.000 claims description 11
- 229940109262 curcumin Drugs 0.000 claims description 11
- 239000004148 curcumin Substances 0.000 claims description 11
- VFLDPWHFBUODDF-UHFFFAOYSA-N diferuloylmethane Natural products C1=C(O)C(OC)=CC(C=CC(=O)CC(=O)C=CC=2C=C(OC)C(O)=CC=2)=C1 VFLDPWHFBUODDF-UHFFFAOYSA-N 0.000 claims description 11
- 201000006417 multiple sclerosis Diseases 0.000 claims description 11
- 208000030507 AIDS Diseases 0.000 claims description 10
- 206010061216 Infarction Diseases 0.000 claims description 10
- 208000028867 ischemia Diseases 0.000 claims description 10
- 229910052727 yttrium Inorganic materials 0.000 claims description 10
- 206010010904 Convulsion Diseases 0.000 claims description 9
- 206010021143 Hypoxia Diseases 0.000 claims description 9
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 9
- 230000036506 anxiety Effects 0.000 claims description 9
- 206010015037 epilepsy Diseases 0.000 claims description 9
- 230000035882 stress Effects 0.000 claims description 9
- OBKXEAXTFZPCHS-UHFFFAOYSA-N 4-phenylbutyric acid Chemical compound OC(=O)CCCC1=CC=CC=C1 OBKXEAXTFZPCHS-UHFFFAOYSA-N 0.000 claims description 8
- 239000005711 Benzoic acid Substances 0.000 claims description 8
- 241001465754 Metazoa Species 0.000 claims description 8
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 8
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 8
- 235000010233 benzoic acid Nutrition 0.000 claims description 8
- 230000008499 blood brain barrier function Effects 0.000 claims description 8
- 210000001218 blood-brain barrier Anatomy 0.000 claims description 8
- 208000004296 neuralgia Diseases 0.000 claims description 8
- 229940127240 opiate Drugs 0.000 claims description 8
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 7
- 208000024827 Alzheimer disease Diseases 0.000 claims description 7
- 206010003591 Ataxia Diseases 0.000 claims description 7
- 208000010412 Glaucoma Diseases 0.000 claims description 7
- 206010047700 Vomiting Diseases 0.000 claims description 7
- 230000002218 hypoglycaemic effect Effects 0.000 claims description 7
- 230000007954 hypoxia Effects 0.000 claims description 7
- 208000015181 infectious disease Diseases 0.000 claims description 7
- 208000021722 neuropathic pain Diseases 0.000 claims description 7
- 229960002715 nicotine Drugs 0.000 claims description 7
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 claims description 7
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 7
- 230000008673 vomiting Effects 0.000 claims description 7
- 208000012661 Dyskinesia Diseases 0.000 claims description 6
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 6
- 208000006011 Stroke Diseases 0.000 claims description 6
- 208000010877 cognitive disease Diseases 0.000 claims description 6
- 206010013663 drug dependence Diseases 0.000 claims description 6
- 210000004962 mammalian cell Anatomy 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 230000029279 positive regulation of transcription, DNA-dependent Effects 0.000 claims description 6
- 208000011117 substance-related disease Diseases 0.000 claims description 6
- 208000028698 Cognitive impairment Diseases 0.000 claims description 5
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 5
- 206010019196 Head injury Diseases 0.000 claims description 5
- 208000010496 Heart Arrest Diseases 0.000 claims description 5
- 208000013016 Hypoglycemia Diseases 0.000 claims description 5
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 5
- 208000019695 Migraine disease Diseases 0.000 claims description 5
- 208000007101 Muscle Cramp Diseases 0.000 claims description 5
- 208000028389 Nerve injury Diseases 0.000 claims description 5
- 208000005392 Spasm Diseases 0.000 claims description 5
- 230000032683 aging Effects 0.000 claims description 5
- 230000005779 cell damage Effects 0.000 claims description 5
- 230000034994 death Effects 0.000 claims description 5
- 230000003111 delayed effect Effects 0.000 claims description 5
- 206010014599 encephalitis Diseases 0.000 claims description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- 208000002780 macular degeneration Diseases 0.000 claims description 5
- 206010027599 migraine Diseases 0.000 claims description 5
- 230000008764 nerve damage Effects 0.000 claims description 5
- 208000005877 painful neuropathy Diseases 0.000 claims description 5
- 208000020431 spinal cord injury Diseases 0.000 claims description 5
- 230000008733 trauma Effects 0.000 claims description 5
- AUQIXRHHSITZFM-UHFFFAOYSA-N 11-phenylundecanoic acid Chemical compound OC(=O)CCCCCCCCCCC1=CC=CC=C1 AUQIXRHHSITZFM-UHFFFAOYSA-N 0.000 claims description 4
- 206010048962 Brain oedema Diseases 0.000 claims description 4
- 208000033892 Hyperhomocysteinemia Diseases 0.000 claims description 4
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 4
- 208000027089 Parkinsonian disease Diseases 0.000 claims description 4
- 206010034010 Parkinsonism Diseases 0.000 claims description 4
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 4
- 208000006752 brain edema Diseases 0.000 claims description 4
- 208000037887 cell injury Diseases 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 125000000219 ethylidene group Chemical group [H]C(=[*])C([H])([H])[H] 0.000 claims description 4
- 230000003225 hyperhomocysteinemia Effects 0.000 claims description 4
- WWZKQHOCKIZLMA-UHFFFAOYSA-N octanoic acid Chemical compound CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 claims description 4
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical compound OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 claims description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 4
- 208000037823 Cerebral ischemia/reperfusion injury Diseases 0.000 claims description 3
- 201000009906 Meningitis Diseases 0.000 claims description 3
- 208000016285 Movement disease Diseases 0.000 claims description 3
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 claims description 3
- 208000017442 Retinal disease Diseases 0.000 claims description 3
- 206010038923 Retinopathy Diseases 0.000 claims description 3
- 206010046543 Urinary incontinence Diseases 0.000 claims description 3
- 238000010171 animal model Methods 0.000 claims description 3
- 230000036461 convulsion Effects 0.000 claims description 3
- 230000001934 delay Effects 0.000 claims description 3
- 238000005462 in vivo assay Methods 0.000 claims description 3
- 208000033300 perinatal asphyxia Diseases 0.000 claims description 3
- 208000032253 retinal ischemia Diseases 0.000 claims description 3
- FJRLRVWAGLLEFU-BLWKUPHCSA-N (2E,6E)-octa-2,6-dienoic acid Chemical compound C\C=C\CC\C=C\C(O)=O FJRLRVWAGLLEFU-BLWKUPHCSA-N 0.000 claims description 2
- IISIYJPTBDSIFM-UHFFFAOYSA-N 10-phenyldecanoic acid Chemical compound OC(=O)CCCCCCCCCC1=CC=CC=C1 IISIYJPTBDSIFM-UHFFFAOYSA-N 0.000 claims description 2
- NNJMFJSKMRYHSR-UHFFFAOYSA-N 4-phenylbenzoic acid Chemical compound C1=CC(C(=O)O)=CC=C1C1=CC=CC=C1 NNJMFJSKMRYHSR-UHFFFAOYSA-N 0.000 claims description 2
- 206010013754 Drug withdrawal syndrome Diseases 0.000 claims description 2
- 208000020564 Eye injury Diseases 0.000 claims description 2
- 208000031886 HIV Infections Diseases 0.000 claims description 2
- 208000037357 HIV infectious disease Diseases 0.000 claims description 2
- OBETXYAYXDNJHR-UHFFFAOYSA-N alpha-ethylcaproic acid Natural products CCCCC(CC)C(O)=O OBETXYAYXDNJHR-UHFFFAOYSA-N 0.000 claims description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 claims description 2
- 201000011475 meningoencephalitis Diseases 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 229960003424 phenylacetic acid Drugs 0.000 claims description 2
- 230000002792 vascular Effects 0.000 claims description 2
- NBBHTEAZLJWUHH-UHFFFAOYSA-N undeca-5,9-dienoic acid Chemical compound CC=CCCC=CCCCC(O)=O NBBHTEAZLJWUHH-UHFFFAOYSA-N 0.000 claims 2
- 230000010354 integration Effects 0.000 claims 1
- 231100000878 neurological injury Toxicity 0.000 claims 1
- 239000002304 perfume Substances 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 58
- 230000001404 mediated effect Effects 0.000 abstract description 20
- 102000040945 Transcription factor Human genes 0.000 abstract description 12
- 229940094443 oxytocics prostaglandins Drugs 0.000 abstract description 6
- 230000014511 neuron projection development Effects 0.000 abstract description 5
- 150000003180 prostaglandins Chemical class 0.000 abstract description 5
- 230000005945 translocation Effects 0.000 abstract description 4
- 101710165986 Negative regulator of transcription Proteins 0.000 abstract 1
- 230000002779 inactivation Effects 0.000 abstract 1
- QRYRORQUOLYVBU-VBKZILBWSA-N carnosic acid Chemical compound CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 277
- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 description 120
- 102000002737 Heme Oxygenase-1 Human genes 0.000 description 105
- 108010018924 Heme Oxygenase-1 Proteins 0.000 description 105
- 239000012039 electrophile Substances 0.000 description 91
- 108700032225 Antioxidant Response Elements Proteins 0.000 description 65
- 230000037361 pathway Effects 0.000 description 62
- 229960003180 glutathione Drugs 0.000 description 59
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 description 50
- 230000004913 activation Effects 0.000 description 47
- 230000006698 induction Effects 0.000 description 43
- 108090000623 proteins and genes Proteins 0.000 description 41
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 31
- 230000001054 cortical effect Effects 0.000 description 30
- 201000010099 disease Diseases 0.000 description 30
- 229930195712 glutamate Natural products 0.000 description 30
- 230000006378 damage Effects 0.000 description 27
- 241000699670 Mus sp. Species 0.000 description 26
- YCIMNLLNPGFGHC-UHFFFAOYSA-N catechol Chemical group OC1=CC=CC=C1O YCIMNLLNPGFGHC-UHFFFAOYSA-N 0.000 description 24
- 208000011580 syndromic disease Diseases 0.000 description 24
- 239000003981 vehicle Substances 0.000 description 22
- 206010008118 cerebral infarction Diseases 0.000 description 21
- 239000004480 active ingredient Substances 0.000 description 20
- 102000004169 proteins and genes Human genes 0.000 description 20
- 230000002829 reductive effect Effects 0.000 description 20
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 19
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 19
- 108010090804 Streptavidin Proteins 0.000 description 19
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 19
- 201000001119 neuropathy Diseases 0.000 description 19
- 235000018102 proteins Nutrition 0.000 description 19
- 230000010410 reperfusion Effects 0.000 description 19
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 18
- BPYKTIZUTYGOLE-IFADSCNNSA-N Bilirubin Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(CC2=C(C(C)=C(\C=C/3C(=C(C=C)C(=O)N\3)C)N2)CCC(O)=O)N1 BPYKTIZUTYGOLE-IFADSCNNSA-N 0.000 description 18
- 229940098773 bovine serum albumin Drugs 0.000 description 18
- 230000007823 neuropathy Effects 0.000 description 18
- 239000004090 neuroprotective agent Substances 0.000 description 18
- 208000033808 peripheral neuropathy Diseases 0.000 description 18
- AZQWKYJCGOJGHM-UHFFFAOYSA-N 1,4-benzoquinone Chemical compound O=C1C=CC(=O)C=C1 AZQWKYJCGOJGHM-UHFFFAOYSA-N 0.000 description 17
- 238000013518 transcription Methods 0.000 description 17
- 230000035897 transcription Effects 0.000 description 17
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 16
- 239000003963 antioxidant agent Substances 0.000 description 16
- 238000006243 chemical reaction Methods 0.000 description 16
- 229910052760 oxygen Inorganic materials 0.000 description 16
- 150000003573 thiols Chemical class 0.000 description 16
- 210000001519 tissue Anatomy 0.000 description 16
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 15
- 230000003078 antioxidant effect Effects 0.000 description 15
- 229960002685 biotin Drugs 0.000 description 15
- 239000011616 biotin Substances 0.000 description 15
- 239000006166 lysate Substances 0.000 description 15
- 235000006708 antioxidants Nutrition 0.000 description 14
- 235000018417 cysteine Nutrition 0.000 description 14
- 125000000151 cysteine group Chemical group N[C@@H](CS)C(=O)* 0.000 description 14
- 238000002474 experimental method Methods 0.000 description 14
- 230000016273 neuron death Effects 0.000 description 14
- 229910052717 sulfur Inorganic materials 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 208000027418 Wounds and injury Diseases 0.000 description 13
- 230000015572 biosynthetic process Effects 0.000 description 13
- 230000002490 cerebral effect Effects 0.000 description 13
- 230000004112 neuroprotection Effects 0.000 description 13
- 230000001590 oxidative effect Effects 0.000 description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 12
- 208000000094 Chronic Pain Diseases 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
- 210000004369 blood Anatomy 0.000 description 12
- 239000008280 blood Substances 0.000 description 12
- 239000013592 cell lysate Substances 0.000 description 12
- XUJNEKJLAYXESH-UHFFFAOYSA-N cysteine Natural products SCC(N)C(O)=O XUJNEKJLAYXESH-UHFFFAOYSA-N 0.000 description 12
- 230000003492 excitotoxic effect Effects 0.000 description 12
- 231100000063 excitotoxicity Toxicity 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 230000007246 mechanism Effects 0.000 description 12
- 239000001301 oxygen Substances 0.000 description 12
- 150000003254 radicals Chemical class 0.000 description 12
- 239000000523 sample Substances 0.000 description 12
- SUVMJBTUFCVSAD-UHFFFAOYSA-N sulforaphane Chemical compound CS(=O)CCCCN=C=S SUVMJBTUFCVSAD-UHFFFAOYSA-N 0.000 description 12
- 238000012360 testing method Methods 0.000 description 12
- 230000002103 transcriptional effect Effects 0.000 description 12
- 201000006474 Brain Ischemia Diseases 0.000 description 11
- 206010008120 Cerebral ischaemia Diseases 0.000 description 11
- XUJNEKJLAYXESH-REOHCLBHSA-N L-Cysteine Chemical compound SC[C@H](N)C(O)=O XUJNEKJLAYXESH-REOHCLBHSA-N 0.000 description 11
- 239000005089 Luciferase Substances 0.000 description 11
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 11
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 11
- HDFGOPSGAURCEO-UHFFFAOYSA-N N-ethylmaleimide Chemical compound CCN1C(=O)C=CC1=O HDFGOPSGAURCEO-UHFFFAOYSA-N 0.000 description 11
- 108091023040 Transcription factor Proteins 0.000 description 11
- 238000009825 accumulation Methods 0.000 description 11
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 11
- 210000003618 cortical neuron Anatomy 0.000 description 11
- 239000002953 phosphate buffered saline Substances 0.000 description 11
- 210000003169 central nervous system Anatomy 0.000 description 10
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 10
- 230000003647 oxidation Effects 0.000 description 10
- 238000007254 oxidation reaction Methods 0.000 description 10
- 239000003642 reactive oxygen metabolite Substances 0.000 description 10
- 125000001424 substituent group Chemical group 0.000 description 10
- 230000001988 toxicity Effects 0.000 description 10
- 231100000419 toxicity Toxicity 0.000 description 10
- 108010024636 Glutathione Proteins 0.000 description 9
- 102000004034 Kelch-Like ECH-Associated Protein 1 Human genes 0.000 description 9
- 108090000484 Kelch-Like ECH-Associated Protein 1 Proteins 0.000 description 9
- 206010033799 Paralysis Diseases 0.000 description 9
- 208000018737 Parkinson disease Diseases 0.000 description 9
- 125000004429 atom Chemical group 0.000 description 9
- 125000000623 heterocyclic group Chemical group 0.000 description 9
- 230000004770 neurodegeneration Effects 0.000 description 9
- 208000015122 neurodegenerative disease Diseases 0.000 description 9
- 230000002887 neurotoxic effect Effects 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 239000000047 product Substances 0.000 description 9
- 230000004044 response Effects 0.000 description 9
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N 1,4-Benzenediol Natural products OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 8
- 230000009471 action Effects 0.000 description 8
- 230000000692 anti-sense effect Effects 0.000 description 8
- 230000001640 apoptogenic effect Effects 0.000 description 8
- 235000020958 biotin Nutrition 0.000 description 8
- 230000001413 cellular effect Effects 0.000 description 8
- 239000003795 chemical substances by application Substances 0.000 description 8
- 230000001419 dependent effect Effects 0.000 description 8
- 238000011161 development Methods 0.000 description 8
- 230000018109 developmental process Effects 0.000 description 8
- 239000002552 dosage form Substances 0.000 description 8
- 238000011534 incubation Methods 0.000 description 8
- 230000007574 infarction Effects 0.000 description 8
- 230000001537 neural effect Effects 0.000 description 8
- 230000001575 pathological effect Effects 0.000 description 8
- 230000004224 protection Effects 0.000 description 8
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 description 8
- 239000000243 solution Substances 0.000 description 8
- 238000010186 staining Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- GWZYPXHJIZCRAJ-UHFFFAOYSA-N Biliverdin Natural products CC1=C(C=C)C(=C/C2=NC(=Cc3[nH]c(C=C/4NC(=O)C(=C4C)C=C)c(C)c3CCC(=O)O)C(=C2C)CCC(=O)O)NC1=O GWZYPXHJIZCRAJ-UHFFFAOYSA-N 0.000 description 7
- RCNSAJSGRJSBKK-NSQVQWHSSA-N Biliverdin IX Chemical compound N1C(=O)C(C)=C(C=C)\C1=C\C1=C(C)C(CCC(O)=O)=C(\C=C/2C(=C(C)C(=C/C=3C(=C(C=C)C(=O)N=3)C)/N\2)CCC(O)=O)N1 RCNSAJSGRJSBKK-NSQVQWHSSA-N 0.000 description 7
- 208000016192 Demyelinating disease Diseases 0.000 description 7
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 7
- 108010081687 Glutamate-cysteine ligase Proteins 0.000 description 7
- 108010053070 Glutathione Disulfide Proteins 0.000 description 7
- 108060001084 Luciferase Proteins 0.000 description 7
- 238000000540 analysis of variance Methods 0.000 description 7
- 230000006907 apoptotic process Effects 0.000 description 7
- QBUVFDKTZJNUPP-UHFFFAOYSA-N biliverdin-IXalpha Natural products N1C(=O)C(C)=C(C=C)C1=CC1=C(C)C(CCC(O)=O)=C(C=C2C(=C(C)C(C=C3C(=C(C=C)C(=O)N3)C)=N2)CCC(O)=O)N1 QBUVFDKTZJNUPP-UHFFFAOYSA-N 0.000 description 7
- 230000004071 biological effect Effects 0.000 description 7
- 208000026106 cerebrovascular disease Diseases 0.000 description 7
- 210000000805 cytoplasm Anatomy 0.000 description 7
- 230000007423 decrease Effects 0.000 description 7
- 231100000673 dose–response relationship Toxicity 0.000 description 7
- 239000003623 enhancer Substances 0.000 description 7
- 239000008103 glucose Substances 0.000 description 7
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 description 7
- 239000005090 green fluorescent protein Substances 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 238000005259 measurement Methods 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- 210000004498 neuroglial cell Anatomy 0.000 description 7
- 231100000252 nontoxic Toxicity 0.000 description 7
- 230000003000 nontoxic effect Effects 0.000 description 7
- 210000000056 organ Anatomy 0.000 description 7
- 150000004053 quinones Chemical class 0.000 description 7
- 210000000278 spinal cord Anatomy 0.000 description 7
- 238000001890 transfection Methods 0.000 description 7
- SUVMJBTUFCVSAD-JTQLQIEISA-N 4-Methylsulfinylbutyl isothiocyanate Natural products C[S@](=O)CCCCN=C=S SUVMJBTUFCVSAD-JTQLQIEISA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 6
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 6
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 206010061218 Inflammation Diseases 0.000 description 6
- 241000699666 Mus <mouse, genus> Species 0.000 description 6
- GHAZCVNUKKZTLG-UHFFFAOYSA-N N-ethyl-succinimide Natural products CCN1C(=O)CCC1=O GHAZCVNUKKZTLG-UHFFFAOYSA-N 0.000 description 6
- 206010028851 Necrosis Diseases 0.000 description 6
- 230000002159 abnormal effect Effects 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 6
- 210000003710 cerebral cortex Anatomy 0.000 description 6
- 239000002299 complementary DNA Substances 0.000 description 6
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 6
- 239000007789 gas Substances 0.000 description 6
- 239000000499 gel Substances 0.000 description 6
- 229910052736 halogen Inorganic materials 0.000 description 6
- 150000002367 halogens Chemical class 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 6
- 230000004054 inflammatory process Effects 0.000 description 6
- 230000003834 intracellular effect Effects 0.000 description 6
- 208000024714 major depressive disease Diseases 0.000 description 6
- 239000002207 metabolite Substances 0.000 description 6
- 230000017074 necrotic cell death Effects 0.000 description 6
- 210000005036 nerve Anatomy 0.000 description 6
- 210000000653 nervous system Anatomy 0.000 description 6
- 238000003757 reverse transcription PCR Methods 0.000 description 6
- 229960005559 sulforaphane Drugs 0.000 description 6
- 235000015487 sulforaphane Nutrition 0.000 description 6
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 description 5
- 208000020401 Depressive disease Diseases 0.000 description 5
- 208000007465 Giant cell arteritis Diseases 0.000 description 5
- 206010019233 Headaches Diseases 0.000 description 5
- 102100028008 Heme oxygenase 2 Human genes 0.000 description 5
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 102100023174 Methionine aminopeptidase 2 Human genes 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- 208000025966 Neurological disease Diseases 0.000 description 5
- 102000003992 Peroxidases Human genes 0.000 description 5
- 241001529742 Rosmarinus Species 0.000 description 5
- 101100221606 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) COS7 gene Proteins 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 230000003213 activating effect Effects 0.000 description 5
- 125000003545 alkoxy group Chemical group 0.000 description 5
- 208000025748 atypical depressive disease Diseases 0.000 description 5
- 210000004204 blood vessel Anatomy 0.000 description 5
- 150000001721 carbon Chemical group 0.000 description 5
- QRYRORQUOLYVBU-YBMSBYLISA-N carnosic acid Chemical compound C1CC2C(C)(C)CCC[C@]2(C(O)=O)C2=C1C=C(C(C)C)C(O)=C2O QRYRORQUOLYVBU-YBMSBYLISA-N 0.000 description 5
- 238000004113 cell culture Methods 0.000 description 5
- 230000001684 chronic effect Effects 0.000 description 5
- 229960003067 cystine Drugs 0.000 description 5
- 238000012217 deletion Methods 0.000 description 5
- 230000037430 deletion Effects 0.000 description 5
- 206010012601 diabetes mellitus Diseases 0.000 description 5
- 239000012636 effector Substances 0.000 description 5
- 235000013305 food Nutrition 0.000 description 5
- 230000006870 function Effects 0.000 description 5
- 102000034356 gene-regulatory proteins Human genes 0.000 description 5
- 108091006104 gene-regulatory proteins Proteins 0.000 description 5
- 231100000869 headache Toxicity 0.000 description 5
- 108010031102 heme oxygenase-2 Proteins 0.000 description 5
- 125000004404 heteroalkyl group Chemical group 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 125000000592 heterocycloalkyl group Chemical group 0.000 description 5
- 238000004128 high performance liquid chromatography Methods 0.000 description 5
- 238000010166 immunofluorescence Methods 0.000 description 5
- 230000001939 inductive effect Effects 0.000 description 5
- 238000003468 luciferase reporter gene assay Methods 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 210000002161 motor neuron Anatomy 0.000 description 5
- 208000005264 motor neuron disease Diseases 0.000 description 5
- 230000000474 nursing effect Effects 0.000 description 5
- 108040007629 peroxidase activity proteins Proteins 0.000 description 5
- 230000002633 protecting effect Effects 0.000 description 5
- 230000001681 protective effect Effects 0.000 description 5
- 230000009467 reduction Effects 0.000 description 5
- 230000002441 reversible effect Effects 0.000 description 5
- 238000002415 sodium dodecyl sulfate polyacrylamide gel electrophoresis Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 150000003505 terpenes Chemical class 0.000 description 5
- 230000001225 therapeutic effect Effects 0.000 description 5
- 238000001262 western blot Methods 0.000 description 5
- CHADEQDQBURGHL-UHFFFAOYSA-N (6'-acetyloxy-3-oxospiro[2-benzofuran-1,9'-xanthene]-3'-yl) acetate Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(OC(C)=O)C=C1OC1=CC(OC(=O)C)=CC=C21 CHADEQDQBURGHL-UHFFFAOYSA-N 0.000 description 4
- PKDBCJSWQUOKDO-UHFFFAOYSA-M 2,3,5-triphenyltetrazolium chloride Chemical compound [Cl-].C1=CC=CC=C1C(N=[N+]1C=2C=CC=CC=2)=NN1C1=CC=CC=C1 PKDBCJSWQUOKDO-UHFFFAOYSA-M 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 4
- 206010002091 Anaesthesia Diseases 0.000 description 4
- 206010010356 Congenital anomaly Diseases 0.000 description 4
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 4
- 238000010867 Hoechst staining Methods 0.000 description 4
- 108090000364 Ligases Proteins 0.000 description 4
- 102000003960 Ligases Human genes 0.000 description 4
- MJVAVZPDRWSRRC-UHFFFAOYSA-N Menadione Chemical compound C1=CC=C2C(=O)C(C)=CC(=O)C2=C1 MJVAVZPDRWSRRC-UHFFFAOYSA-N 0.000 description 4
- LOUPRKONTZGTKE-WZBLMQSHSA-N Quinine Chemical compound C([C@H]([C@H](C1)C=C)C2)C[N@@]1[C@@H]2[C@H](O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-WZBLMQSHSA-N 0.000 description 4
- 206010063837 Reperfusion injury Diseases 0.000 description 4
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 230000029936 alkylation Effects 0.000 description 4
- 238000005804 alkylation reaction Methods 0.000 description 4
- 125000003277 amino group Chemical group 0.000 description 4
- 230000037005 anaesthesia Effects 0.000 description 4
- 230000017531 blood circulation Effects 0.000 description 4
- 230000036772 blood pressure Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 244000309464 bull Species 0.000 description 4
- 230000015556 catabolic process Effects 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 239000006185 dispersion Substances 0.000 description 4
- 239000013604 expression vector Substances 0.000 description 4
- 210000001508 eye Anatomy 0.000 description 4
- 229930003935 flavonoid Natural products 0.000 description 4
- 235000017173 flavonoids Nutrition 0.000 description 4
- 150000003278 haem Chemical class 0.000 description 4
- 125000001188 haloalkyl group Chemical group 0.000 description 4
- 238000001114 immunoprecipitation Methods 0.000 description 4
- 238000001802 infusion Methods 0.000 description 4
- 238000002347 injection Methods 0.000 description 4
- 239000007924 injection Substances 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 210000003657 middle cerebral artery Anatomy 0.000 description 4
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 4
- 210000003205 muscle Anatomy 0.000 description 4
- 230000035772 mutation Effects 0.000 description 4
- 230000009223 neuronal apoptosis Effects 0.000 description 4
- 231100000189 neurotoxic Toxicity 0.000 description 4
- 210000000578 peripheral nerve Anatomy 0.000 description 4
- 239000000546 pharmaceutical excipient Substances 0.000 description 4
- 239000013612 plasmid Substances 0.000 description 4
- 230000003389 potentiating effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- XJMOSONTPMZWPB-UHFFFAOYSA-M propidium iodide Chemical compound [I-].[I-].C12=CC(N)=CC=C2C2=CC=C(N)C=C2[N+](CCC[N+](C)(CC)CC)=C1C1=CC=CC=C1 XJMOSONTPMZWPB-UHFFFAOYSA-M 0.000 description 4
- 230000001105 regulatory effect Effects 0.000 description 4
- 238000003571 reporter gene assay Methods 0.000 description 4
- JUVIOZPCNVVQFO-UHFFFAOYSA-N rotenone Natural products O1C2=C3CC(C(C)=C)OC3=CC=C2C(=O)C2C1COC1=C2C=C(OC)C(OC)=C1 JUVIOZPCNVVQFO-UHFFFAOYSA-N 0.000 description 4
- 229940080817 rotenone Drugs 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 201000000980 schizophrenia Diseases 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000035945 sensitivity Effects 0.000 description 4
- 210000002966 serum Anatomy 0.000 description 4
- 230000019491 signal transduction Effects 0.000 description 4
- 210000003625 skull Anatomy 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- 239000011593 sulfur Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 230000004083 survival effect Effects 0.000 description 4
- 239000003826 tablet Substances 0.000 description 4
- 206010043207 temporal arteritis Diseases 0.000 description 4
- QAIPRVGONGVQAS-DUXPYHPUSA-N trans-caffeic acid Chemical compound OC(=O)\C=C\C1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-DUXPYHPUSA-N 0.000 description 4
- 239000013598 vector Substances 0.000 description 4
- 101150028074 2 gene Proteins 0.000 description 3
- DJQYYYCQOZMCRC-UHFFFAOYSA-N 2-aminopropane-1,3-dithiol Chemical compound SCC(N)CS DJQYYYCQOZMCRC-UHFFFAOYSA-N 0.000 description 3
- AZKSAVLVSZKNRD-UHFFFAOYSA-M 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide Chemical compound [Br-].S1C(C)=C(C)N=C1[N+]1=NC(C=2C=CC=CC=2)=NN1C1=CC=CC=C1 AZKSAVLVSZKNRD-UHFFFAOYSA-M 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 102100026189 Beta-galactosidase Human genes 0.000 description 3
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- 208000014644 Brain disease Diseases 0.000 description 3
- 239000004215 Carbon black (E152) Substances 0.000 description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 3
- XUSYGBPHQBWGAD-PJSUUKDQSA-N Carnosol Chemical compound CC([C@@H]1C2)(C)CCC[C@@]11C(=O)O[C@@H]2C2=C1C(O)=C(O)C(C(C)C)=C2 XUSYGBPHQBWGAD-PJSUUKDQSA-N 0.000 description 3
- 208000018652 Closed Head injury Diseases 0.000 description 3
- 208000014094 Dystonic disease Diseases 0.000 description 3
- 239000012594 Earle’s Balanced Salt Solution Substances 0.000 description 3
- 208000032274 Encephalopathy Diseases 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 108090000331 Firefly luciferases Proteins 0.000 description 3
- 108010010803 Gelatin Proteins 0.000 description 3
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 3
- 208000007514 Herpes zoster Diseases 0.000 description 3
- 241000282412 Homo Species 0.000 description 3
- 101001092197 Homo sapiens RNA binding protein fox-1 homolog 3 Proteins 0.000 description 3
- 239000012097 Lipofectamine 2000 Substances 0.000 description 3
- 108090000192 Methionyl aminopeptidases Proteins 0.000 description 3
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 3
- 208000019022 Mood disease Diseases 0.000 description 3
- 102100021339 Multidrug resistance-associated protein 1 Human genes 0.000 description 3
- 208000001089 Multiple system atrophy Diseases 0.000 description 3
- 101100338009 Mus musculus Gsta1 gene Proteins 0.000 description 3
- 208000008238 Muscle Spasticity Diseases 0.000 description 3
- 206010028570 Myelopathy Diseases 0.000 description 3
- 206010028813 Nausea Diseases 0.000 description 3
- 206010030113 Oedema Diseases 0.000 description 3
- 208000003435 Optic Neuritis Diseases 0.000 description 3
- 206010031127 Orthostatic hypotension Diseases 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100035530 RNA binding protein fox-1 homolog 3 Human genes 0.000 description 3
- 208000005587 Refsum Disease Diseases 0.000 description 3
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 3
- 102100036407 Thioredoxin Human genes 0.000 description 3
- 208000000323 Tourette Syndrome Diseases 0.000 description 3
- 208000016620 Tourette disease Diseases 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 239000002671 adjuvant Substances 0.000 description 3
- 125000003282 alkyl amino group Chemical group 0.000 description 3
- 229940100198 alkylating agent Drugs 0.000 description 3
- 239000002168 alkylating agent Substances 0.000 description 3
- 125000000304 alkynyl group Chemical group 0.000 description 3
- 229940035676 analgesics Drugs 0.000 description 3
- 239000005557 antagonist Substances 0.000 description 3
- 239000000730 antalgic agent Substances 0.000 description 3
- 239000001961 anticonvulsive agent Substances 0.000 description 3
- 239000002246 antineoplastic agent Substances 0.000 description 3
- 239000002249 anxiolytic agent Substances 0.000 description 3
- 238000013459 approach Methods 0.000 description 3
- 210000003403 autonomic nervous system Anatomy 0.000 description 3
- 230000004900 autophagic degradation Effects 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 230000008901 benefit Effects 0.000 description 3
- 108010005774 beta-Galactosidase Proteins 0.000 description 3
- 230000033228 biological regulation Effects 0.000 description 3
- 230000036770 blood supply Effects 0.000 description 3
- 208000029028 brain injury Diseases 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 125000001589 carboacyl group Chemical group 0.000 description 3
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 230000003833 cell viability Effects 0.000 description 3
- 206010008129 cerebral palsy Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- NKLPQNGYXWVELD-UHFFFAOYSA-M coomassie brilliant blue Chemical compound [Na+].C1=CC(OCC)=CC=C1NC1=CC=C(C(=C2C=CC(C=C2)=[N+](CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=2C=CC(=CC=2)N(CC)CC=2C=C(C=CC=2)S([O-])(=O)=O)C=C1 NKLPQNGYXWVELD-UHFFFAOYSA-M 0.000 description 3
- 125000004093 cyano group Chemical group *C#N 0.000 description 3
- 230000001120 cytoprotective effect Effects 0.000 description 3
- 230000001086 cytosolic effect Effects 0.000 description 3
- 210000001787 dendrite Anatomy 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- 229960003638 dopamine Drugs 0.000 description 3
- 229960004679 doxorubicin Drugs 0.000 description 3
- 230000008451 emotion Effects 0.000 description 3
- 210000003414 extremity Anatomy 0.000 description 3
- 210000000744 eyelid Anatomy 0.000 description 3
- 206010016256 fatigue Diseases 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 108010068906 gamma-glutamylcysteine Proteins 0.000 description 3
- 239000008273 gelatin Substances 0.000 description 3
- 229920000159 gelatin Polymers 0.000 description 3
- 235000019322 gelatine Nutrition 0.000 description 3
- 235000011852 gelatine desserts Nutrition 0.000 description 3
- 125000005843 halogen group Chemical group 0.000 description 3
- 229930195733 hydrocarbon Natural products 0.000 description 3
- 239000001257 hydrogen Substances 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 230000005764 inhibitory process Effects 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 230000002427 irreversible effect Effects 0.000 description 3
- 201000010901 lateral sclerosis Diseases 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 210000002418 meninge Anatomy 0.000 description 3
- 230000037353 metabolic pathway Effects 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 230000036651 mood Effects 0.000 description 3
- 108010066052 multidrug resistance-associated protein 1 Proteins 0.000 description 3
- 230000008693 nausea Effects 0.000 description 3
- 230000000926 neurological effect Effects 0.000 description 3
- 230000004792 oxidative damage Effects 0.000 description 3
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
- 230000003076 paracrine Effects 0.000 description 3
- 230000036961 partial effect Effects 0.000 description 3
- 210000001428 peripheral nervous system Anatomy 0.000 description 3
- 125000003367 polycyclic group Chemical group 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000003752 polymerase chain reaction Methods 0.000 description 3
- 239000002243 precursor Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000001737 promoting effect Effects 0.000 description 3
- 208000020016 psychiatric disease Diseases 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000000306 recurrent effect Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 210000001525 retina Anatomy 0.000 description 3
- 239000001296 salvia officinalis l. Substances 0.000 description 3
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 3
- 230000035939 shock Effects 0.000 description 3
- 150000003384 small molecules Chemical class 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 208000018198 spasticity Diseases 0.000 description 3
- 238000003860 storage Methods 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- 239000004094 surface-active agent Substances 0.000 description 3
- 230000035900 sweating Effects 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000009885 systemic effect Effects 0.000 description 3
- 229940124597 therapeutic agent Drugs 0.000 description 3
- 125000004149 thio group Chemical group *S* 0.000 description 3
- 108060008226 thioredoxin Proteins 0.000 description 3
- 230000000472 traumatic effect Effects 0.000 description 3
- 238000011144 upstream manufacturing Methods 0.000 description 3
- 230000035899 viability Effects 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- ACEAELOMUCBPJP-UHFFFAOYSA-N (E)-3,4,5-trihydroxycinnamic acid Natural products OC(=O)C=CC1=CC(O)=C(O)C(O)=C1 ACEAELOMUCBPJP-UHFFFAOYSA-N 0.000 description 2
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 2
- FTEGUKWEUQPKIS-UHFFFAOYSA-N 1,5-bis(4-hydroxyphenyl)penta-1,4-dien-3-one Chemical compound C1=CC(O)=CC=C1C=CC(=O)C=CC1=CC=C(O)C=C1 FTEGUKWEUQPKIS-UHFFFAOYSA-N 0.000 description 2
- FCEHBMOGCRZNNI-UHFFFAOYSA-N 1-benzothiophene Chemical compound C1=CC=C2SC=CC2=C1 FCEHBMOGCRZNNI-UHFFFAOYSA-N 0.000 description 2
- TUXFWOHFPFBNEJ-GJGHEGAFSA-N 13,14-dihydro-Delta(12)-prostaglandin J2 Chemical compound CCCCC[C@H](O)C\C=C1/[C@@H](C\C=C/CCCC(O)=O)C=CC1=O TUXFWOHFPFBNEJ-GJGHEGAFSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- 208000004998 Abdominal Pain Diseases 0.000 description 2
- 229920000936 Agarose Polymers 0.000 description 2
- 102000003669 Antiporters Human genes 0.000 description 2
- 108090000084 Antiporters Proteins 0.000 description 2
- 206010003101 Arnold-Chiari Malformation Diseases 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- 206010003694 Atrophy Diseases 0.000 description 2
- 102000008836 BTB/POZ domains Human genes 0.000 description 2
- 208000008035 Back Pain Diseases 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 241000167854 Bourreria succulenta Species 0.000 description 2
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 description 2
- MMFRMKXYTWBMOM-UHFFFAOYSA-N Carnosol Natural products CCc1cc2C3CC4C(C)(C)CCCC4(C(=O)O3)c2c(O)c1O MMFRMKXYTWBMOM-UHFFFAOYSA-N 0.000 description 2
- 102100025064 Cellular tumor antigen p53 Human genes 0.000 description 2
- 208000015321 Chiari malformation Diseases 0.000 description 2
- 206010008748 Chorea Diseases 0.000 description 2
- 235000001258 Cinchona calisaya Nutrition 0.000 description 2
- 206010010071 Coma Diseases 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 108010072220 Cyclophilin A Proteins 0.000 description 2
- 206010012335 Dependence Diseases 0.000 description 2
- 206010012374 Depressed mood Diseases 0.000 description 2
- 208000027534 Emotional disease Diseases 0.000 description 2
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- 229930091371 Fructose Natural products 0.000 description 2
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 2
- 108700039691 Genetic Promoter Regions Proteins 0.000 description 2
- 102000018899 Glutamate Receptors Human genes 0.000 description 2
- 108010027915 Glutamate Receptors Proteins 0.000 description 2
- 102100039696 Glutamate-cysteine ligase catalytic subunit Human genes 0.000 description 2
- 239000004471 Glycine Substances 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- 208000002972 Hepatolenticular Degeneration Diseases 0.000 description 2
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 2
- 101000721661 Homo sapiens Cellular tumor antigen p53 Proteins 0.000 description 2
- 101000979001 Homo sapiens Methionine aminopeptidase 2 Proteins 0.000 description 2
- 101000969087 Homo sapiens Microtubule-associated protein 2 Proteins 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 238000012404 In vitro experiment Methods 0.000 description 2
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 231100000002 MTT assay Toxicity 0.000 description 2
- 238000000134 MTT assay Methods 0.000 description 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 102220477667 Mitochondrial inner membrane protease subunit 2_S40T_mutation Human genes 0.000 description 2
- 201000002169 Mitochondrial myopathy Diseases 0.000 description 2
- 241000699660 Mus musculus Species 0.000 description 2
- 208000021642 Muscular disease Diseases 0.000 description 2
- 102000006386 Myelin Proteins Human genes 0.000 description 2
- 108010083674 Myelin Proteins Proteins 0.000 description 2
- 101710161549 NADPH quinone oxidoreductase Proteins 0.000 description 2
- 102000003945 NF-kappa B Human genes 0.000 description 2
- 108010057466 NF-kappa B Proteins 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 206010029216 Nervousness Diseases 0.000 description 2
- 206010029240 Neuritis Diseases 0.000 description 2
- 208000008457 Neurologic Manifestations Diseases 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- GQPLMRYTRLFLPF-UHFFFAOYSA-N Nitrous Oxide Chemical compound [O-][N+]#N GQPLMRYTRLFLPF-UHFFFAOYSA-N 0.000 description 2
- 108091034117 Oligonucleotide Proteins 0.000 description 2
- 208000005225 Opsoclonus-Myoclonus Syndrome Diseases 0.000 description 2
- 206010033885 Paraparesis Diseases 0.000 description 2
- 208000000450 Pelvic Pain Diseases 0.000 description 2
- 102100034539 Peptidyl-prolyl cis-trans isomerase A Human genes 0.000 description 2
- 102000003728 Peroxisome Proliferator-Activated Receptors Human genes 0.000 description 2
- 108090000029 Peroxisome Proliferator-Activated Receptors Proteins 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- 229920001213 Polysorbate 20 Polymers 0.000 description 2
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 2
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 2
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 description 2
- 208000028017 Psychotic disease Diseases 0.000 description 2
- 108700008625 Reporter Genes Proteins 0.000 description 2
- 244000178231 Rosmarinus officinalis Species 0.000 description 2
- 229920002684 Sepharose Polymers 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 241000534944 Thia Species 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 101710168651 Thioredoxin 1 Proteins 0.000 description 2
- 206010044074 Torticollis Diseases 0.000 description 2
- 208000030886 Traumatic Brain injury Diseases 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 208000003443 Unconsciousness Diseases 0.000 description 2
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 241000700605 Viruses Species 0.000 description 2
- 208000018839 Wilson disease Diseases 0.000 description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 230000005856 abnormality Effects 0.000 description 2
- 238000010521 absorption reaction Methods 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 239000012190 activator Substances 0.000 description 2
- 230000009056 active transport Effects 0.000 description 2
- 125000004442 acylamino group Chemical group 0.000 description 2
- ORILYTVJVMAKLC-UHFFFAOYSA-N adamantane Chemical compound C1C(C2)CC3CC1CC2C3 ORILYTVJVMAKLC-UHFFFAOYSA-N 0.000 description 2
- 102000035181 adaptor proteins Human genes 0.000 description 2
- 108091005764 adaptor proteins Proteins 0.000 description 2
- 208000030597 adult Refsum disease Diseases 0.000 description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 description 2
- 125000004414 alkyl thio group Chemical group 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 150000001450 anions Chemical class 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 230000002924 anti-infective effect Effects 0.000 description 2
- 230000000561 anti-psychotic effect Effects 0.000 description 2
- 230000000949 anxiolytic effect Effects 0.000 description 2
- 125000003435 aroyl group Chemical group 0.000 description 2
- 230000004872 arterial blood pressure Effects 0.000 description 2
- 125000005110 aryl thio group Chemical group 0.000 description 2
- 125000004104 aryloxy group Chemical group 0.000 description 2
- 235000010357 aspartame Nutrition 0.000 description 2
- 230000037444 atrophy Effects 0.000 description 2
- 230000002567 autonomic effect Effects 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 125000004619 benzopyranyl group Chemical group O1C(C=CC2=C1C=CC=C2)* 0.000 description 2
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 2
- 239000002876 beta blocker Substances 0.000 description 2
- 125000002619 bicyclic group Chemical group 0.000 description 2
- 230000007321 biological mechanism Effects 0.000 description 2
- 239000000872 buffer Substances 0.000 description 2
- 235000004883 caffeic acid Nutrition 0.000 description 2
- 229940074360 caffeic acid Drugs 0.000 description 2
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 2
- 235000004654 carnosol Nutrition 0.000 description 2
- 210000000170 cell membrane Anatomy 0.000 description 2
- 210000004671 cell-free system Anatomy 0.000 description 2
- 230000004700 cellular uptake Effects 0.000 description 2
- 230000003727 cerebral blood flow Effects 0.000 description 2
- 239000003638 chemical reducing agent Substances 0.000 description 2
- 230000001767 chemoprotection Effects 0.000 description 2
- 235000019693 cherries Nutrition 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- HVYWMOMLDIMFJA-DPAQBDIFSA-N cholesterol Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H]([C@H](C)CCCC(C)C)[C@@]1(C)CC2 HVYWMOMLDIMFJA-DPAQBDIFSA-N 0.000 description 2
- LOUPRKONTZGTKE-UHFFFAOYSA-N cinchonine Natural products C1C(C(C2)C=C)CCN2C1C(O)C1=CC=NC2=CC=C(OC)C=C21 LOUPRKONTZGTKE-UHFFFAOYSA-N 0.000 description 2
- QAIPRVGONGVQAS-UHFFFAOYSA-N cis-caffeic acid Natural products OC(=O)C=CC1=CC=C(O)C(O)=C1 QAIPRVGONGVQAS-UHFFFAOYSA-N 0.000 description 2
- 238000012761 co-transfection Methods 0.000 description 2
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 230000036757 core body temperature Effects 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 210000003792 cranial nerve Anatomy 0.000 description 2
- 150000001945 cysteines Chemical class 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 230000007547 defect Effects 0.000 description 2
- 230000007123 defense Effects 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- 229960002069 diamorphine Drugs 0.000 description 2
- 235000005911 diet Nutrition 0.000 description 2
- 230000037213 diet Effects 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- 125000004982 dihaloalkyl group Chemical group 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 229930004069 diterpene Natural products 0.000 description 2
- 208000002173 dizziness Diseases 0.000 description 2
- 230000004064 dysfunction Effects 0.000 description 2
- 208000024732 dysthymic disease Diseases 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- 230000002996 emotional effect Effects 0.000 description 2
- 201000002491 encephalomyelitis Diseases 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- MHMNJMPURVTYEJ-UHFFFAOYSA-N fluorescein-5-isothiocyanate Chemical compound O1C(=O)C2=CC(N=C=S)=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 MHMNJMPURVTYEJ-UHFFFAOYSA-N 0.000 description 2
- 235000003599 food sweetener Nutrition 0.000 description 2
- 239000008098 formaldehyde solution Substances 0.000 description 2
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 108020001507 fusion proteins Proteins 0.000 description 2
- 102000037865 fusion proteins Human genes 0.000 description 2
- 150000002334 glycols Chemical class 0.000 description 2
- 229940093915 gynecological organic acid Drugs 0.000 description 2
- 125000004438 haloalkoxy group Chemical group 0.000 description 2
- 230000000147 hypnotic effect Effects 0.000 description 2
- 238000010191 image analysis Methods 0.000 description 2
- 238000012744 immunostaining Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 208000023692 inborn mitochondrial myopathy Diseases 0.000 description 2
- 210000003000 inclusion body Anatomy 0.000 description 2
- 239000000411 inducer Substances 0.000 description 2
- 230000004941 influx Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 208000018197 inherited torticollis Diseases 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- SUMDYPCJJOFFON-UHFFFAOYSA-N isethionic acid Chemical compound OCCS(O)(=O)=O SUMDYPCJJOFFON-UHFFFAOYSA-N 0.000 description 2
- 229960002725 isoflurane Drugs 0.000 description 2
- 231100000859 kill neurons Toxicity 0.000 description 2
- 238000011813 knockout mouse model Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 208000036546 leukodystrophy Diseases 0.000 description 2
- 125000005647 linker group Chemical group 0.000 description 2
- 239000002502 liposome Substances 0.000 description 2
- 239000011777 magnesium Substances 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 230000009525 mild injury Effects 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 230000004065 mitochondrial dysfunction Effects 0.000 description 2
- 125000002950 monocyclic group Chemical group 0.000 description 2
- 229960005181 morphine Drugs 0.000 description 2
- 230000004118 muscle contraction Effects 0.000 description 2
- 229940035363 muscle relaxants Drugs 0.000 description 2
- 210000005012 myelin Anatomy 0.000 description 2
- 239000003158 myorelaxant agent Substances 0.000 description 2
- 201000003631 narcolepsy Diseases 0.000 description 2
- 208000020470 nervous system symptom Diseases 0.000 description 2
- 230000003961 neuronal insult Effects 0.000 description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 2
- 230000005937 nuclear translocation Effects 0.000 description 2
- 230000000269 nucleophilic effect Effects 0.000 description 2
- 231100000862 numbness Toxicity 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 208000021090 palsy Diseases 0.000 description 2
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 2
- 230000002093 peripheral effect Effects 0.000 description 2
- 230000002085 persistent effect Effects 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 125000006684 polyhaloalkyl group Polymers 0.000 description 2
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 2
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 239000003223 protective agent Substances 0.000 description 2
- 125000004076 pyridyl group Chemical group 0.000 description 2
- 229960000948 quinine Drugs 0.000 description 2
- 239000002516 radical scavenger Substances 0.000 description 2
- 238000009790 rate-determining step (RDS) Methods 0.000 description 2
- 230000006697 redox regulation Effects 0.000 description 2
- BOLDJAUMGUJJKM-LSDHHAIUSA-N renifolin D Natural products CC(=C)[C@@H]1Cc2c(O)c(O)ccc2[C@H]1CC(=O)c3ccc(O)cc3O BOLDJAUMGUJJKM-LSDHHAIUSA-N 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 206010039073 rheumatoid arthritis Diseases 0.000 description 2
- 235000015639 rosmarinus officinalis Nutrition 0.000 description 2
- 235000002020 sage Nutrition 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 2
- 210000004761 scalp Anatomy 0.000 description 2
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 2
- 230000035807 sensation Effects 0.000 description 2
- 235000019615 sensations Nutrition 0.000 description 2
- 230000001953 sensory effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000007858 starting material Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical compound OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 125000000475 sulfinyl group Chemical group [*:2]S([*:1])=O 0.000 description 2
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 2
- 150000003457 sulfones Chemical class 0.000 description 2
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 239000003765 sweetening agent Substances 0.000 description 2
- 206010042772 syncope Diseases 0.000 description 2
- 239000006188 syrup Substances 0.000 description 2
- 235000020357 syrup Nutrition 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- 238000011830 transgenic mouse model Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- URAYPUMNDPQOKB-UHFFFAOYSA-N triacetin Chemical compound CC(=O)OCC(OC(C)=O)COC(C)=O URAYPUMNDPQOKB-UHFFFAOYSA-N 0.000 description 2
- 230000009107 upstream regulation Effects 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- 235000012711 vitamin K3 Nutrition 0.000 description 2
- 239000011652 vitamin K3 Substances 0.000 description 2
- 229940041603 vitamin k 3 Drugs 0.000 description 2
- 238000009736 wetting Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 0.000 description 2
- FUTVBRXUIKZACV-UHFFFAOYSA-L zinc;3-[18-(2-carboxyethyl)-8,13-bis(ethenyl)-3,7,12,17-tetramethylporphyrin-21,23-diid-2-yl]propanoic acid Chemical compound [Zn+2].[N-]1C(C=C2C(=C(C=C)C(C=C3C(=C(C=C)C(=C4)[N-]3)C)=N2)C)=C(C)C(CCC(O)=O)=C1C=C1C(CCC(O)=O)=C(C)C4=N1 FUTVBRXUIKZACV-UHFFFAOYSA-L 0.000 description 2
- 150000008505 β-D-glucopyranosides Chemical class 0.000 description 2
- KYZWKYWGQFCRGN-OASOTCBPSA-N (2s)-2-aminopentanedioic acid;(2r)-2-(methylamino)butanedioic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O.OC(=O)[C@@H](N)CCC(O)=O KYZWKYWGQFCRGN-OASOTCBPSA-N 0.000 description 1
- RLCKHJSFHOZMDR-UHFFFAOYSA-N (3R, 7R, 11R)-1-Phytanoid acid Natural products CC(C)CCCC(C)CCCC(C)CCCC(C)CC(O)=O RLCKHJSFHOZMDR-UHFFFAOYSA-N 0.000 description 1
- NJZHEQOUHLZCOX-ZENOOKHLSA-N (3aR,4R,9bS)-golgicide A Chemical compound C1([C@@H]2NC3=C(F)C=C(C=C3[C@H]3C=CC[C@H]32)F)=CC=CN=C1 NJZHEQOUHLZCOX-ZENOOKHLSA-N 0.000 description 1
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- UWYVPFMHMJIBHE-OWOJBTEDSA-N (e)-2-hydroxybut-2-enedioic acid Chemical compound OC(=O)\C=C(\O)C(O)=O UWYVPFMHMJIBHE-OWOJBTEDSA-N 0.000 description 1
- VHRUMKCAEVRUBK-WKELIDJCSA-N (z)-7-[(1s,5e)-5-[(z)-oct-2-enylidene]-4-oxocyclopent-2-en-1-yl]hept-5-enoic acid Chemical compound CCCCC\C=C/C=C1\[C@@H](C\C=C/CCCC(O)=O)C=CC1=O VHRUMKCAEVRUBK-WKELIDJCSA-N 0.000 description 1
- POPHMOPNVVKGRW-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydronaphthalene Chemical compound C1CCC2CCCCC2=C1 POPHMOPNVVKGRW-UHFFFAOYSA-N 0.000 description 1
- AEERSNXTBVFRMQ-UHFFFAOYSA-N 1,2-dihydrophenanthrene-1-carboxylic acid Chemical compound C1=CC2=CC=CC=C2C2=C1C(C(=O)O)CC=C2 AEERSNXTBVFRMQ-UHFFFAOYSA-N 0.000 description 1
- 125000005871 1,3-benzodioxolyl group Chemical group 0.000 description 1
- IGERFAHWSHDDHX-UHFFFAOYSA-N 1,3-dioxanyl Chemical group [CH]1OCCCO1 IGERFAHWSHDDHX-UHFFFAOYSA-N 0.000 description 1
- JPRPJUMQRZTTED-UHFFFAOYSA-N 1,3-dioxolanyl Chemical group [CH]1OCCO1 JPRPJUMQRZTTED-UHFFFAOYSA-N 0.000 description 1
- 125000005940 1,4-dioxanyl group Chemical group 0.000 description 1
- YNPNZTXNASCQKK-UICOGKGYSA-N 1-deuteriophenanthrene Chemical compound C1=CC2=CC=CC=C2C2=C1C([2H])=CC=C2 YNPNZTXNASCQKK-UICOGKGYSA-N 0.000 description 1
- ZAUYNCUCMJDAHW-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;hydrogen peroxide;molecular iodine Chemical compound OO.II.C=CN1CCCC1=O ZAUYNCUCMJDAHW-UHFFFAOYSA-N 0.000 description 1
- FGOJCPKOOGIRPA-UHFFFAOYSA-N 1-o-tert-butyl 4-o-ethyl 5-oxoazepane-1,4-dicarboxylate Chemical compound CCOC(=O)C1CCN(C(=O)OC(C)(C)C)CCC1=O FGOJCPKOOGIRPA-UHFFFAOYSA-N 0.000 description 1
- GUNGXQJKXNQLMP-UHFFFAOYSA-N 11,12,16-Trihydroxy-8,11,13-abietatrien-20-oic acid Natural products CC(CO)c1cc2CCC3C(C)(C)CCCC3(C(=O)O)c2c(O)c1O GUNGXQJKXNQLMP-UHFFFAOYSA-N 0.000 description 1
- HYZJCKYKOHLVJF-UHFFFAOYSA-N 1H-benzimidazole Chemical compound C1=CC=C2NC=NC2=C1 HYZJCKYKOHLVJF-UHFFFAOYSA-N 0.000 description 1
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 description 1
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 description 1
- PWVRXSQPCQPQHM-UHFFFAOYSA-N 2-(4-aminophenyl)-1h-indol-6-amine Chemical compound C1=CC(N)=CC=C1C1=CC2=CC=C(N)C=C2N1 PWVRXSQPCQPQHM-UHFFFAOYSA-N 0.000 description 1
- LBLYYCQCTBFVLH-UHFFFAOYSA-N 2-Methylbenzenesulfonic acid Chemical compound CC1=CC=CC=C1S(O)(=O)=O LBLYYCQCTBFVLH-UHFFFAOYSA-N 0.000 description 1
- WXHLLJAMBQLULT-UHFFFAOYSA-N 2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-n-(2-methyl-6-sulfanylphenyl)-1,3-thiazole-5-carboxamide;hydrate Chemical compound O.C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1S WXHLLJAMBQLULT-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- SNBCLPGEMZEWLU-QXFUBDJGSA-N 2-chloro-n-[[(2r,3s,5r)-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl]acetamide Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CNC(=O)CCl)[C@@H](O)C1 SNBCLPGEMZEWLU-QXFUBDJGSA-N 0.000 description 1
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 1
- MHIITNFQDPFSES-UHFFFAOYSA-N 25,26,27,28-tetrazahexacyclo[16.6.1.13,6.18,11.113,16.019,24]octacosa-1(25),2,4,6,8(27),9,11,13,15,17,19,21,23-tridecaene Chemical compound N1C(C=C2C3=CC=CC=C3C(C=C3NC(=C4)C=C3)=N2)=CC=C1C=C1C=CC4=N1 MHIITNFQDPFSES-UHFFFAOYSA-N 0.000 description 1
- COXZITOAYLSIFO-UHFFFAOYSA-N 2h-phenanthrene-1,4a-dicarboxylic acid Chemical compound C1=CC2=CC=CC=C2C2(C(O)=O)C1=C(C(=O)O)CC=C2 COXZITOAYLSIFO-UHFFFAOYSA-N 0.000 description 1
- RLCKHJSFHOZMDR-PWCSWUJKSA-N 3,7R,11R,15-tetramethyl-hexadecanoic acid Chemical compound CC(C)CCC[C@@H](C)CCC[C@@H](C)CCCC(C)CC(O)=O RLCKHJSFHOZMDR-PWCSWUJKSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 206010065040 AIDS dementia complex Diseases 0.000 description 1
- 102100024643 ATP-binding cassette sub-family D member 1 Human genes 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 206010054196 Affect lability Diseases 0.000 description 1
- 208000006888 Agnosia Diseases 0.000 description 1
- 241001047040 Agnosia Species 0.000 description 1
- 208000024341 Aicardi syndrome Diseases 0.000 description 1
- 208000011403 Alexander disease Diseases 0.000 description 1
- 208000023434 Alpers-Huttenlocher syndrome Diseases 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- 208000031277 Amaurotic familial idiocy Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 208000031091 Amnestic disease Diseases 0.000 description 1
- 208000009575 Angelman syndrome Diseases 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 206010059245 Angiopathy Diseases 0.000 description 1
- 206010002660 Anoxia Diseases 0.000 description 1
- 241000976983 Anoxia Species 0.000 description 1
- 102100021569 Apoptosis regulator Bcl-2 Human genes 0.000 description 1
- 206010003062 Apraxia Diseases 0.000 description 1
- 208000022316 Arachnoid cyst Diseases 0.000 description 1
- 208000022211 Arteriovenous Malformations Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 208000036640 Asperger disease Diseases 0.000 description 1
- 201000006062 Asperger syndrome Diseases 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 241000416162 Astragalus gummifer Species 0.000 description 1
- 102000007371 Ataxin-3 Human genes 0.000 description 1
- 201000001320 Atherosclerosis Diseases 0.000 description 1
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 1
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 108090001008 Avidin Proteins 0.000 description 1
- 208000035143 Bacterial infection Diseases 0.000 description 1
- 102100026596 Bcl-2-like protein 1 Human genes 0.000 description 1
- 208000009137 Behcet syndrome Diseases 0.000 description 1
- 208000034577 Benign intracranial hypertension Diseases 0.000 description 1
- 102100022548 Beta-hexosaminidase subunit alpha Human genes 0.000 description 1
- 206010006074 Brachial plexus injury Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- 101100348867 Caenorhabditis elegans nep-11 gene Proteins 0.000 description 1
- 208000022526 Canavan disease Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 108010087806 Carnosine Proteins 0.000 description 1
- 102000003952 Caspase 3 Human genes 0.000 description 1
- 108090000397 Caspase 3 Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102100035882 Catalase Human genes 0.000 description 1
- 108010053835 Catalase Proteins 0.000 description 1
- 206010064012 Central pain syndrome Diseases 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 206010008027 Cerebellar atrophy Diseases 0.000 description 1
- 206010065559 Cerebral arteriosclerosis Diseases 0.000 description 1
- 206010008096 Cerebral atrophy Diseases 0.000 description 1
- 208000018152 Cerebral disease Diseases 0.000 description 1
- 206010008111 Cerebral haemorrhage Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 206010008479 Chest Pain Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010008874 Chronic Fatigue Syndrome Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- 241000723346 Cinnamomum camphora Species 0.000 description 1
- 108091062157 Cis-regulatory element Proteins 0.000 description 1
- 208000002881 Colic Diseases 0.000 description 1
- 208000013586 Complex regional pain syndrome type 1 Diseases 0.000 description 1
- 102000012437 Copper-Transporting ATPases Human genes 0.000 description 1
- 208000011990 Corticobasal Degeneration Diseases 0.000 description 1
- 208000019736 Cranial nerve disease Diseases 0.000 description 1
- 208000020406 Creutzfeldt Jacob disease Diseases 0.000 description 1
- 208000003407 Creutzfeldt-Jakob Syndrome Diseases 0.000 description 1
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 description 1
- 208000012514 Cumulative Trauma disease Diseases 0.000 description 1
- 244000163122 Curcuma domestica Species 0.000 description 1
- 208000014311 Cushing syndrome Diseases 0.000 description 1
- 108010068192 Cyclin A Proteins 0.000 description 1
- 108010060385 Cyclin B1 Proteins 0.000 description 1
- 102100025191 Cyclin-A2 Human genes 0.000 description 1
- 241001044073 Cypa Species 0.000 description 1
- 206010011732 Cyst Diseases 0.000 description 1
- 102100030497 Cytochrome c Human genes 0.000 description 1
- 108010075031 Cytochromes c Proteins 0.000 description 1
- 206010011831 Cytomegalovirus infection Diseases 0.000 description 1
- VVNCNSJFMMFHPL-VKHMYHEASA-N D-penicillamine Chemical group CC(C)(S)[C@@H](N)C(O)=O VVNCNSJFMMFHPL-VKHMYHEASA-N 0.000 description 1
- 102000053602 DNA Human genes 0.000 description 1
- 230000005778 DNA damage Effects 0.000 description 1
- 231100000277 DNA damage Toxicity 0.000 description 1
- 201000003863 Dandy-Walker Syndrome Diseases 0.000 description 1
- 206010012239 Delusion Diseases 0.000 description 1
- 206010012305 Demyelination Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 1
- QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 1
- 208000004986 Diffuse Cerebral Sclerosis of Schilder Diseases 0.000 description 1
- 208000003164 Diplopia Diseases 0.000 description 1
- 208000007590 Disorders of Excessive Somnolence Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 206010013887 Dysarthria Diseases 0.000 description 1
- 206010058314 Dysplasia Diseases 0.000 description 1
- 241001317099 Dystaxia Species 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 201000008009 Early infantile epileptic encephalopathy Diseases 0.000 description 1
- 208000002403 Encephalocele Diseases 0.000 description 1
- 241000283086 Equidae Species 0.000 description 1
- 206010015719 Exsanguination Diseases 0.000 description 1
- 101710131282 FAD-linked oxidoreductase easE Proteins 0.000 description 1
- 208000024720 Fabry Disease Diseases 0.000 description 1
- 208000004929 Facial Paralysis Diseases 0.000 description 1
- 208000002091 Febrile Seizures Diseases 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- 102100032340 G2/mitotic-specific cyclin-B1 Human genes 0.000 description 1
- 206010017577 Gait disturbance Diseases 0.000 description 1
- 208000015872 Gaucher disease Diseases 0.000 description 1
- 208000011688 Generalised anxiety disease Diseases 0.000 description 1
- 108700028146 Genetic Enhancer Elements Proteins 0.000 description 1
- 201000004311 Gilles de la Tourette syndrome Diseases 0.000 description 1
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 208000010055 Globoid Cell Leukodystrophy Diseases 0.000 description 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
- 102000017278 Glutaredoxin Human genes 0.000 description 1
- 108050005205 Glutaredoxin Proteins 0.000 description 1
- 101710171252 Glutaredoxin-1 Proteins 0.000 description 1
- 108010070675 Glutathione transferase Proteins 0.000 description 1
- 208000009396 Group II Malformations of Cortical Development Diseases 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000004547 Hallucinations Diseases 0.000 description 1
- 208000013875 Heart injury Diseases 0.000 description 1
- 102100029100 Hematopoietic prostaglandin D synthase Human genes 0.000 description 1
- 208000004095 Hemifacial Spasm Diseases 0.000 description 1
- 208000028782 Hereditary disease Diseases 0.000 description 1
- 206010063491 Herpes zoster oticus Diseases 0.000 description 1
- 208000017605 Hodgkin disease nodular sclerosis Diseases 0.000 description 1
- 101000971171 Homo sapiens Apoptosis regulator Bcl-2 Proteins 0.000 description 1
- 101100456626 Homo sapiens MEF2A gene Proteins 0.000 description 1
- 101000956263 Homo sapiens Uncharacterized protein C19orf48 Proteins 0.000 description 1
- 108010001336 Horseradish Peroxidase Proteins 0.000 description 1
- 241000714260 Human T-lymphotropic virus 1 Species 0.000 description 1
- 208000008454 Hyperhidrosis Diseases 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 206010020772 Hypertension Diseases 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- 208000018127 Idiopathic intracranial hypertension Diseases 0.000 description 1
- 206010021402 Illogical thinking Diseases 0.000 description 1
- 206010021750 Infantile Spasms Diseases 0.000 description 1
- 208000035899 Infantile spasms syndrome Diseases 0.000 description 1
- 201000006347 Intellectual Disability Diseases 0.000 description 1
- 102000003996 Interferon-beta Human genes 0.000 description 1
- 108090000467 Interferon-beta Proteins 0.000 description 1
- 208000005615 Interstitial Cystitis Diseases 0.000 description 1
- 208000018650 Intervertebral disc disease Diseases 0.000 description 1
- 206010022773 Intracranial pressure increased Diseases 0.000 description 1
- 206010022998 Irritability Diseases 0.000 description 1
- 108010044467 Isoenzymes Proteins 0.000 description 1
- 208000027747 Kennedy disease Diseases 0.000 description 1
- 208000028226 Krabbe disease Diseases 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- FFFHZYDWPBMWHY-VKHMYHEASA-N L-homocysteine Chemical compound OC(=O)[C@@H](N)CCS FFFHZYDWPBMWHY-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 208000005870 Lafora disease Diseases 0.000 description 1
- 208000014161 Lafora myoclonic epilepsy Diseases 0.000 description 1
- 201000005802 Landau-Kleffner Syndrome Diseases 0.000 description 1
- 208000020358 Learning disease Diseases 0.000 description 1
- 208000009625 Lesch-Nyhan syndrome Diseases 0.000 description 1
- 206010024264 Lethargy Diseases 0.000 description 1
- URLZCHNOLZSCCA-VABKMULXSA-N Leu-enkephalin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)CNC(=O)CNC(=O)[C@@H](N)CC=1C=CC(O)=CC=1)C1=CC=CC=C1 URLZCHNOLZSCCA-VABKMULXSA-N 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 201000002832 Lewy body dementia Diseases 0.000 description 1
- 208000008930 Low Back Pain Diseases 0.000 description 1
- 208000016604 Lyme disease Diseases 0.000 description 1
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 102000039538 Maf family Human genes 0.000 description 1
- 108091067370 Maf family Proteins 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 201000005505 Measles Diseases 0.000 description 1
- 108010049137 Member 1 Subfamily D ATP Binding Cassette Transporter Proteins 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 208000008948 Menkes Kinky Hair Syndrome Diseases 0.000 description 1
- 208000012583 Menkes disease Diseases 0.000 description 1
- 244000246386 Mentha pulegium Species 0.000 description 1
- 235000016257 Mentha pulegium Nutrition 0.000 description 1
- 235000004357 Mentha x piperita Nutrition 0.000 description 1
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
- 101710094503 Metallothionein-1 Proteins 0.000 description 1
- 102100031347 Metallothionein-2 Human genes 0.000 description 1
- 101710094505 Metallothionein-2 Proteins 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 201000002983 Mobius syndrome Diseases 0.000 description 1
- 208000034167 Moebius syndrome Diseases 0.000 description 1
- 229940123685 Monoamine oxidase inhibitor Drugs 0.000 description 1
- 206010069681 Monomelic amyotrophy Diseases 0.000 description 1
- 208000019430 Motor disease Diseases 0.000 description 1
- 206010061296 Motor dysfunction Diseases 0.000 description 1
- 208000026072 Motor neurone disease Diseases 0.000 description 1
- 208000009433 Moyamoya Disease Diseases 0.000 description 1
- 208000002678 Mucopolysaccharidoses Diseases 0.000 description 1
- 208000002430 Multiple chemical sensitivity Diseases 0.000 description 1
- 101001079625 Mus musculus Heme oxygenase 1 Proteins 0.000 description 1
- 101100079042 Mus musculus Myef2 gene Proteins 0.000 description 1
- 208000010428 Muscle Weakness Diseases 0.000 description 1
- 206010028289 Muscle atrophy Diseases 0.000 description 1
- 208000029578 Muscle disease Diseases 0.000 description 1
- 206010028347 Muscle twitching Diseases 0.000 description 1
- 206010028372 Muscular weakness Diseases 0.000 description 1
- 208000036572 Myoclonic epilepsy Diseases 0.000 description 1
- 102100021148 Myocyte-specific enhancer factor 2A Human genes 0.000 description 1
- 201000009623 Myopathy Diseases 0.000 description 1
- 201000002481 Myositis Diseases 0.000 description 1
- 206010061533 Myotonia Diseases 0.000 description 1
- 208000010316 Myotonia congenita Diseases 0.000 description 1
- 208000012905 Myotonic disease Diseases 0.000 description 1
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 description 1
- 150000001204 N-oxides Chemical class 0.000 description 1
- 206010028836 Neck pain Diseases 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 208000009905 Neurofibromatoses Diseases 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 208000002537 Neuronal Ceroid-Lipofuscinoses Diseases 0.000 description 1
- 206010029350 Neurotoxicity Diseases 0.000 description 1
- 208000014060 Niemann-Pick disease Diseases 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 239000000020 Nitrocellulose Substances 0.000 description 1
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 208000020265 O'Sullivan-McLeod syndrome Diseases 0.000 description 1
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 1
- 206010068106 Occipital neuralgia Diseases 0.000 description 1
- 240000007817 Olea europaea Species 0.000 description 1
- 108700020796 Oncogene Proteins 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- 206010053854 Opsoclonus myoclonus Diseases 0.000 description 1
- 101710199728 Oxidoreductase 1 Proteins 0.000 description 1
- 102000004316 Oxidoreductases Human genes 0.000 description 1
- 108090000854 Oxidoreductases Proteins 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- 108091007960 PI3Ks Proteins 0.000 description 1
- 102000025443 POZ domain binding proteins Human genes 0.000 description 1
- 108091014659 POZ domain binding proteins Proteins 0.000 description 1
- 206010033433 Pain in jaw Diseases 0.000 description 1
- 206010056332 Panencephalitis Diseases 0.000 description 1
- 229930040373 Paraformaldehyde Natural products 0.000 description 1
- 208000031481 Pathologic Constriction Diseases 0.000 description 1
- 208000037273 Pathologic Processes Diseases 0.000 description 1
- 208000028361 Penetrating Head injury Diseases 0.000 description 1
- 108010038988 Peptide Hormones Proteins 0.000 description 1
- 102000015731 Peptide Hormones Human genes 0.000 description 1
- 208000010886 Peripheral nerve injury Diseases 0.000 description 1
- 206010034620 Peripheral sensory neuropathy Diseases 0.000 description 1
- 208000012202 Pervasive developmental disease Diseases 0.000 description 1
- 208000004983 Phantom Limb Diseases 0.000 description 1
- 206010034912 Phobia Diseases 0.000 description 1
- 102000003993 Phosphatidylinositol 3-kinases Human genes 0.000 description 1
- 108090000430 Phosphatidylinositol 3-kinases Proteins 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 1
- 208000024571 Pick disease Diseases 0.000 description 1
- 208000007913 Pituitary Neoplasms Diseases 0.000 description 1
- 101000708422 Podarcis siculus Tissue- and phase-specific nuclear protein Proteins 0.000 description 1
- 208000010366 Postpoliomyelitis syndrome Diseases 0.000 description 1
- 201000010769 Prader-Willi syndrome Diseases 0.000 description 1
- 208000027030 Premenstrual dysphoric disease Diseases 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- 208000024777 Prion disease Diseases 0.000 description 1
- 208000037534 Progressive hemifacial atrophy Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 108010029485 Protein Isoforms Proteins 0.000 description 1
- 102000001708 Protein Isoforms Human genes 0.000 description 1
- 206010037660 Pyrexia Diseases 0.000 description 1
- 239000012083 RIPA buffer Substances 0.000 description 1
- 206010071141 Rasmussen encephalitis Diseases 0.000 description 1
- 208000004160 Rasmussen subacute encephalitis Diseases 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 201000001947 Reflex Sympathetic Dystrophy Diseases 0.000 description 1
- 206010038584 Repetitive strain injury Diseases 0.000 description 1
- 206010038687 Respiratory distress Diseases 0.000 description 1
- 108091027981 Response element Proteins 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 201000007527 Retinal artery occlusion Diseases 0.000 description 1
- 208000006289 Rett Syndrome Diseases 0.000 description 1
- 201000007981 Reye syndrome Diseases 0.000 description 1
- 125000005631 S-sulfonamido group Chemical group 0.000 description 1
- 239000012722 SDS sample buffer Substances 0.000 description 1
- 240000007164 Salvia officinalis Species 0.000 description 1
- 235000002912 Salvia officinalis Nutrition 0.000 description 1
- 238000010165 Scheffé test Methods 0.000 description 1
- MTCFGRXMJLQNBG-UHFFFAOYSA-N Serine Natural products OCC(N)C(O)=O MTCFGRXMJLQNBG-UHFFFAOYSA-N 0.000 description 1
- 229920001800 Shellac Polymers 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- 208000021386 Sjogren Syndrome Diseases 0.000 description 1
- 206010041415 Spastic paralysis Diseases 0.000 description 1
- 201000010829 Spina bifida Diseases 0.000 description 1
- 208000029033 Spinal Cord disease Diseases 0.000 description 1
- 208000006097 Spinal Dysraphism Diseases 0.000 description 1
- 206010041549 Spinal cord compression Diseases 0.000 description 1
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 101100054666 Streptomyces halstedii sch3 gene Proteins 0.000 description 1
- 208000010513 Stupor Diseases 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- 102000019197 Superoxide Dismutase Human genes 0.000 description 1
- 108010012715 Superoxide dismutase Proteins 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 206010042928 Syringomyelia Diseases 0.000 description 1
- 206010042953 Systemic sclerosis Diseases 0.000 description 1
- 210000001744 T-lymphocyte Anatomy 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 208000034799 Tauopathies Diseases 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 206010043189 Telangiectasia Diseases 0.000 description 1
- 208000008548 Tension-Type Headache Diseases 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 description 1
- 208000035317 Total hypoxanthine-guanine phosphoribosyl transferase deficiency Diseases 0.000 description 1
- 206010044221 Toxic encephalopathy Diseases 0.000 description 1
- 229920001615 Tragacanth Polymers 0.000 description 1
- 108010018242 Transcription Factor AP-1 Proteins 0.000 description 1
- 108700009124 Transcription Initiation Site Proteins 0.000 description 1
- 102100023132 Transcription factor Jun Human genes 0.000 description 1
- 208000032109 Transient ischaemic attack Diseases 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 239000013504 Triton X-100 Substances 0.000 description 1
- 229920004890 Triton X-100 Polymers 0.000 description 1
- 206010044696 Tropical spastic paresis Diseases 0.000 description 1
- 102100031988 Tumor necrosis factor ligand superfamily member 6 Human genes 0.000 description 1
- 108050002568 Tumor necrosis factor ligand superfamily member 6 Proteins 0.000 description 1
- 108090000848 Ubiquitin Proteins 0.000 description 1
- 102000044159 Ubiquitin Human genes 0.000 description 1
- 102100038573 Uncharacterized protein C19orf48 Human genes 0.000 description 1
- 208000036826 VIIth nerve paralysis Diseases 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 206010047115 Vasculitis Diseases 0.000 description 1
- 208000036142 Viral infection Diseases 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010047531 Visual acuity reduced Diseases 0.000 description 1
- 208000035562 Wallenberg syndrome Diseases 0.000 description 1
- 201000006791 West syndrome Diseases 0.000 description 1
- 206010049644 Williams syndrome Diseases 0.000 description 1
- 208000013142 Writer cramp Diseases 0.000 description 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- XJLXINKUBYWONI-DQQFMEOOSA-N [[(2r,3r,4r,5r)-5-(6-aminopurin-9-yl)-3-hydroxy-4-phosphonooxyoxolan-2-yl]methoxy-hydroxyphosphoryl] [(2s,3r,4s,5s)-5-(3-carbamoylpyridin-1-ium-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl phosphate Chemical compound NC(=O)C1=CC=C[N+]([C@@H]2[C@H]([C@@H](O)[C@H](COP([O-])(=O)OP(O)(=O)OC[C@@H]3[C@H]([C@@H](OP(O)(O)=O)[C@@H](O3)N3C4=NC=NC(N)=C4N=C3)O)O2)O)=C1 XJLXINKUBYWONI-DQQFMEOOSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 238000001467 acupuncture Methods 0.000 description 1
- 208000002552 acute disseminated encephalomyelitis Diseases 0.000 description 1
- 208000005298 acute pain Diseases 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 208000012826 adjustment disease Diseases 0.000 description 1
- 239000000464 adrenergic agent Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 206010064930 age-related macular degeneration Diseases 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 125000004450 alkenylene group Chemical group 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000004644 alkyl sulfinyl group Chemical group 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000005012 alkyl thioether group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 125000001118 alkylidene group Chemical group 0.000 description 1
- 125000004419 alkynylene group Chemical group 0.000 description 1
- 208000030961 allergic reaction Diseases 0.000 description 1
- HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 1
- 208000011916 alternating hemiplegia Diseases 0.000 description 1
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000006986 amnesia Effects 0.000 description 1
- 230000003321 amplification Effects 0.000 description 1
- 210000003484 anatomy Anatomy 0.000 description 1
- 230000007953 anoxia Effects 0.000 description 1
- 125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000002424 anti-apoptotic effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 230000003474 anti-emetic effect Effects 0.000 description 1
- 230000001384 anti-glaucoma Effects 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 230000000340 anti-metabolite Effects 0.000 description 1
- 229940035678 anti-parkinson drug Drugs 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 229940125713 antianxiety drug Drugs 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 239000002111 antiemetic agent Substances 0.000 description 1
- 229940125683 antiemetic agent Drugs 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940127088 antihypertensive drug Drugs 0.000 description 1
- 229940100197 antimetabolite Drugs 0.000 description 1
- 239000002256 antimetabolite Substances 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229940005530 anxiolytics Drugs 0.000 description 1
- 201000007201 aphasia Diseases 0.000 description 1
- 230000005775 apoptotic pathway Effects 0.000 description 1
- 230000004596 appetite loss Effects 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000005744 arteriovenous malformation Effects 0.000 description 1
- 206010003246 arthritis Diseases 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 125000005015 aryl alkynyl group Chemical group 0.000 description 1
- 125000001769 aryl amino group Chemical group 0.000 description 1
- 150000005840 aryl radicals Chemical class 0.000 description 1
- 125000005135 aryl sulfinyl group Chemical group 0.000 description 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 229960003438 aspartame Drugs 0.000 description 1
- 206010003549 asthenia Diseases 0.000 description 1
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 1
- 208000029560 autism spectrum disease Diseases 0.000 description 1
- 210000000467 autonomic pathway Anatomy 0.000 description 1
- 208000031375 autosomal dominant myotonia congenita Diseases 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 125000002393 azetidinyl group Chemical group 0.000 description 1
- 125000004069 aziridinyl group Chemical group 0.000 description 1
- 125000003828 azulenyl group Chemical group 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 208000022362 bacterial infectious disease Diseases 0.000 description 1
- 239000003855 balanced salt solution Substances 0.000 description 1
- 229940125717 barbiturate Drugs 0.000 description 1
- HNYOPLTXPVRDBG-UHFFFAOYSA-N barbituric acid Chemical compound O=C1CC(=O)NC(=O)N1 HNYOPLTXPVRDBG-UHFFFAOYSA-N 0.000 description 1
- 239000011324 bead Substances 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000005605 benzo group Chemical group 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 125000002047 benzodioxolyl group Chemical group O1OC(C2=C1C=CC=C2)* 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 229960004365 benzoic acid Drugs 0.000 description 1
- 125000005874 benzothiadiazolyl group Chemical group 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000003354 benzotriazolyl group Chemical group N1N=NC2=C1C=CC=C2* 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- MKCBRYIXFFGIKN-UHFFFAOYSA-N bicyclo[1.1.1]pentane Chemical compound C1C2CC1C2 MKCBRYIXFFGIKN-UHFFFAOYSA-N 0.000 description 1
- LPCWKMYWISGVSK-UHFFFAOYSA-N bicyclo[3.2.1]octane Chemical compound C1C2CCC1CCC2 LPCWKMYWISGVSK-UHFFFAOYSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003851 biochemical process Effects 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 239000012503 blood component Substances 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 210000000988 bone and bone Anatomy 0.000 description 1
- 230000006931 brain damage Effects 0.000 description 1
- 231100000874 brain damage Toxicity 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 210000000133 brain stem Anatomy 0.000 description 1
- 238000009395 breeding Methods 0.000 description 1
- 230000001488 breeding effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- 239000006189 buccal tablet Substances 0.000 description 1
- 210000005252 bulbus oculi Anatomy 0.000 description 1
- 230000001201 calcium accumulation Effects 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 229960000846 camphor Drugs 0.000 description 1
- 229930008380 camphor Natural products 0.000 description 1
- 208000035269 cancer or benign tumor Diseases 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 125000000609 carbazolyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3NC12)* 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 238000012754 cardiac puncture Methods 0.000 description 1
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 description 1
- 229940044199 carnosine Drugs 0.000 description 1
- 208000003295 carpal tunnel syndrome Diseases 0.000 description 1
- 150000003943 catecholamines Chemical class 0.000 description 1
- 238000010822 cell death assay Methods 0.000 description 1
- 230000003915 cell function Effects 0.000 description 1
- 239000002771 cell marker Substances 0.000 description 1
- 230000005889 cellular cytotoxicity Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 229940124444 chemoprotective agent Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 239000007958 cherry flavor Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 235000012000 cholesterol Nutrition 0.000 description 1
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 208000012601 choreatic disease Diseases 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000004617 chromonyl group Chemical group O1C(=CC(C2=CC=CC=C12)=O)* 0.000 description 1
- 201000005795 chronic inflammatory demyelinating polyneuritis Diseases 0.000 description 1
- 230000006726 chronic neurodegeneration Effects 0.000 description 1
- 230000004087 circulation Effects 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 208000035850 clinical syndrome Diseases 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 238000000749 co-immunoprecipitation Methods 0.000 description 1
- 238000000576 coating method Methods 0.000 description 1
- 229960003920 cocaine Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 230000004456 color vision Effects 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 230000002301 combined effect Effects 0.000 description 1
- 239000000306 component Substances 0.000 description 1
- 229940125904 compound 1 Drugs 0.000 description 1
- 229940125782 compound 2 Drugs 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 229940125898 compound 5 Drugs 0.000 description 1
- 230000006835 compression Effects 0.000 description 1
- 238000007906 compression Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 235000008504 concentrate Nutrition 0.000 description 1
- 230000009514 concussion Effects 0.000 description 1
- 239000000039 congener Substances 0.000 description 1
- 230000001268 conjugating effect Effects 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 230000002920 convulsive effect Effects 0.000 description 1
- 229940038717 copaxone Drugs 0.000 description 1
- 210000000877 corpus callosum Anatomy 0.000 description 1
- 125000000332 coumarinyl group Chemical group O1C(=O)C(=CC2=CC=CC=C12)* 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 235000003373 curcuma longa Nutrition 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 208000031513 cyst Diseases 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 231100000135 cytotoxicity Toxicity 0.000 description 1
- 230000003013 cytotoxicity Effects 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 230000006735 deficit Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 231100000868 delusion Toxicity 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 230000000779 depleting effect Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 201000001981 dermatomyositis Diseases 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 208000013257 developmental and epileptic encephalopathy Diseases 0.000 description 1
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 1
- 229940038472 dicalcium phosphate Drugs 0.000 description 1
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 1
- 125000003963 dichloro group Chemical group Cl* 0.000 description 1
- 125000006003 dichloroethyl group Chemical group 0.000 description 1
- 125000004774 dichlorofluoromethyl group Chemical group FC(Cl)(Cl)* 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000006001 difluoroethyl group Chemical group 0.000 description 1
- LTVOKYUPTHZZQH-UHFFFAOYSA-N difluoromethane Chemical group F[C]F LTVOKYUPTHZZQH-UHFFFAOYSA-N 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 125000005433 dihydrobenzodioxinyl group Chemical group O1C(COC2=C1C=CC=C2)* 0.000 description 1
- 125000001070 dihydroindolyl group Chemical group N1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000004611 dihydroisoindolyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000005045 dihydroisoquinolinyl group Chemical group C1(NC=CC2=CC=CC=C12)* 0.000 description 1
- 125000004655 dihydropyridinyl group Chemical group N1(CC=CC=C1)* 0.000 description 1
- UGMCXQCYOVCMTB-UHFFFAOYSA-K dihydroxy(stearato)aluminium Chemical compound CCCCCCCCCCCCCCCCCC(=O)O[Al](O)O UGMCXQCYOVCMTB-UHFFFAOYSA-K 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- LDCRTTXIJACKKU-ONEGZZNKSA-N dimethyl fumarate Chemical compound COC(=O)\C=C\C(=O)OC LDCRTTXIJACKKU-ONEGZZNKSA-N 0.000 description 1
- 229960004419 dimethyl fumarate Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002612 dispersion medium Substances 0.000 description 1
- 150000004141 diterpene derivatives Chemical class 0.000 description 1
- 125000000567 diterpene group Chemical group 0.000 description 1
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- 239000003596 drug target Substances 0.000 description 1
- 206010013932 dyslexia Diseases 0.000 description 1
- 150000002066 eicosanoids Chemical class 0.000 description 1
- 230000004970 emotional disturbance Effects 0.000 description 1
- 230000006397 emotional response Effects 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 210000002472 endoplasmic reticulum Anatomy 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 238000001952 enzyme assay Methods 0.000 description 1
- 238000001317 epifluorescence microscopy Methods 0.000 description 1
- 201000006517 essential tremor Diseases 0.000 description 1
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000005678 ethenylene group Chemical group [H]C([*:1])=C([H])[*:2] 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 125000005677 ethinylene group Chemical group [*:2]C#C[*:1] 0.000 description 1
- 125000004494 ethyl ester group Chemical group 0.000 description 1
- 125000004672 ethylcarbonyl group Chemical group [H]C([H])([H])C([H])([H])C(*)=O 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 230000002461 excitatory amino acid Effects 0.000 description 1
- 239000003257 excitatory amino acid Substances 0.000 description 1
- 239000004060 excitotoxin Substances 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- 230000001815 facial effect Effects 0.000 description 1
- 208000002980 facial hemiatrophy Diseases 0.000 description 1
- 235000013861 fat-free Nutrition 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 210000001105 femoral artery Anatomy 0.000 description 1
- 239000012091 fetal bovine serum Substances 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000003527 fibrinolytic agent Substances 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 125000004216 fluoromethyl group Chemical group [H]C([H])(F)* 0.000 description 1
- 201000002865 focal hand dystonia Diseases 0.000 description 1
- HKIOYBQGHSTUDB-UHFFFAOYSA-N folpet Chemical group C1=CC=C2C(=O)N(SC(Cl)(Cl)Cl)C(=O)C2=C1 HKIOYBQGHSTUDB-UHFFFAOYSA-N 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 230000007760 free radical scavenging Effects 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004612 furopyridinyl group Chemical group O1C(=CC2=C1C=CC=N2)* 0.000 description 1
- ZZUFCTLCJUWOSV-UHFFFAOYSA-N furosemide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC(C(O)=O)=C1NCC1=CC=CO1 ZZUFCTLCJUWOSV-UHFFFAOYSA-N 0.000 description 1
- 230000004927 fusion Effects 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 230000005021 gait Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 238000003209 gene knockout Methods 0.000 description 1
- 208000029364 generalized anxiety disease Diseases 0.000 description 1
- 201000011349 geniculate herpes zoster Diseases 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 239000004220 glutamic acid Substances 0.000 description 1
- 235000013922 glutamic acid Nutrition 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- 125000005908 glyceryl ester group Chemical group 0.000 description 1
- 239000001087 glyceryl triacetate Substances 0.000 description 1
- 235000013773 glyceryl triacetate Nutrition 0.000 description 1
- 210000002288 golgi apparatus Anatomy 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 208000035474 group of disease Diseases 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- UYTPUPDQBNUYGX-UHFFFAOYSA-N guanine Chemical group O=C1NC(N)=NC2=C1N=CN2 UYTPUPDQBNUYGX-UHFFFAOYSA-N 0.000 description 1
- 239000000380 hallucinogen Substances 0.000 description 1
- 125000000262 haloalkenyl group Chemical group 0.000 description 1
- 125000000232 haloalkynyl group Chemical group 0.000 description 1
- 210000003128 head Anatomy 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 229910001385 heavy metal Inorganic materials 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- 235000001050 hortel pimenta Nutrition 0.000 description 1
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 description 1
- 229940091173 hydantoin Drugs 0.000 description 1
- 125000000717 hydrazino group Chemical group [H]N([*])N([H])[H] 0.000 description 1
- 208000003906 hydrocephalus Diseases 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 206010020765 hypersomnia Diseases 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000001146 hypoxic effect Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 238000003119 immunoblot Methods 0.000 description 1
- 238000003365 immunocytochemistry Methods 0.000 description 1
- 238000003125 immunofluorescent labeling Methods 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 201000008319 inclusion body myositis Diseases 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 206010021654 increased appetite Diseases 0.000 description 1
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 1
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 239000007972 injectable composition Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 230000037041 intracellular level Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 201000005851 intracranial arteriosclerosis Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 230000003447 ipsilateral effect Effects 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 230000000302 ischemic effect Effects 0.000 description 1
- 229940045996 isethionic acid Drugs 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000004594 isoindolinyl group Chemical group C1(NCC2=CC=CC=C12)* 0.000 description 1
- 125000000904 isoindolyl group Chemical group C=1(NC=C2C=CC=CC12)* 0.000 description 1
- XVQUOJBERHHONY-UHFFFAOYSA-N isometheptene Chemical compound CNC(C)CCC=C(C)C XVQUOJBERHHONY-UHFFFAOYSA-N 0.000 description 1
- 229960003046 isometheptene Drugs 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000005956 isoquinolyl group Chemical group 0.000 description 1
- 125000001786 isothiazolyl group Chemical group 0.000 description 1
- 150000002540 isothiocyanates Chemical class 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000002045 lasting effect Effects 0.000 description 1
- 208000004343 lateral medullary syndrome Diseases 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- XMGQYMWWDOXHJM-UHFFFAOYSA-N limonene Chemical compound CC(=C)C1CCC(C)=CC1 XMGQYMWWDOXHJM-UHFFFAOYSA-N 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 208000019017 loss of appetite Diseases 0.000 description 1
- 235000021266 loss of appetite Nutrition 0.000 description 1
- 231100000875 loss of motor control Toxicity 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 230000036244 malformation Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 230000003211 malignant effect Effects 0.000 description 1
- 239000003550 marker Substances 0.000 description 1
- 230000018984 mastication Effects 0.000 description 1
- 238000010077 mastication Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 101150014102 mef-2 gene Proteins 0.000 description 1
- 201000003995 melancholia Diseases 0.000 description 1
- BUGYDGFZZOZRHP-UHFFFAOYSA-N memantine Chemical compound C1C(C2)CC3(C)CC1(C)CC2(N)C3 BUGYDGFZZOZRHP-UHFFFAOYSA-N 0.000 description 1
- 229960004640 memantine Drugs 0.000 description 1
- 206010027175 memory impairment Diseases 0.000 description 1
- 230000006996 mental state Effects 0.000 description 1
- 108020004999 messenger RNA Proteins 0.000 description 1
- 229960001797 methadone Drugs 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- OSWPMRLSEDHDFF-UHFFFAOYSA-N methyl salicylate Chemical compound COC(=O)C1=CC=CC=C1O OSWPMRLSEDHDFF-UHFFFAOYSA-N 0.000 description 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 description 1
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 1
- 208000004141 microcephaly Diseases 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 230000027939 micturition Effects 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 230000005787 mitochondrial ATP synthesis coupled electron transport Effects 0.000 description 1
- 201000011540 mitochondrial DNA depletion syndrome 4a Diseases 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 230000004769 mitochondrial stress Effects 0.000 description 1
- 230000037230 mobility Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 239000002899 monoamine oxidase inhibitor Substances 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000006682 monohaloalkyl group Chemical group 0.000 description 1
- 230000002969 morbid Effects 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 238000010172 mouse model Methods 0.000 description 1
- 206010028093 mucopolysaccharidosis Diseases 0.000 description 1
- 206010065579 multifocal motor neuropathy Diseases 0.000 description 1
- 230000020763 muscle atrophy Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 201000006938 muscular dystrophy Diseases 0.000 description 1
- 208000029766 myalgic encephalomeyelitis/chronic fatigue syndrome Diseases 0.000 description 1
- 210000003007 myelin sheath Anatomy 0.000 description 1
- 230000023105 myelination Effects 0.000 description 1
- LNOPIUAQISRISI-UHFFFAOYSA-N n'-hydroxy-2-propan-2-ylsulfonylethanimidamide Chemical compound CC(C)S(=O)(=O)CC(N)=NO LNOPIUAQISRISI-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001038 naphthoyl group Chemical group C1(=CC=CC2=CC=CC=C12)C(=O)* 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 210000003061 neural cell Anatomy 0.000 description 1
- 201000010193 neural tube defect Diseases 0.000 description 1
- 201000004931 neurofibromatosis Diseases 0.000 description 1
- 239000003176 neuroleptic agent Substances 0.000 description 1
- 230000000701 neuroleptic effect Effects 0.000 description 1
- 230000002232 neuromuscular Effects 0.000 description 1
- 208000013315 neuromuscular junction disease Diseases 0.000 description 1
- 201000008051 neuronal ceroid lipofuscinosis Diseases 0.000 description 1
- 230000007512 neuronal protection Effects 0.000 description 1
- 230000006576 neuronal survival Effects 0.000 description 1
- 231100000228 neurotoxicity Toxicity 0.000 description 1
- 230000007135 neurotoxicity Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229930027945 nicotinamide-adenine dinucleotide Natural products 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 229920001220 nitrocellulos Polymers 0.000 description 1
- 239000001272 nitrous oxide Substances 0.000 description 1
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000012457 nonaqueous media Substances 0.000 description 1
- 231100000028 nontoxic concentration Toxicity 0.000 description 1
- 230000004493 normal intraocular pressure Effects 0.000 description 1
- 101150075804 nqo1 gene Proteins 0.000 description 1
- 238000003199 nucleic acid amplification method Methods 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 210000003733 optic disk Anatomy 0.000 description 1
- 239000007968 orange flavor Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 125000001715 oxadiazolyl group Chemical group 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 125000002971 oxazolyl group Chemical group 0.000 description 1
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 description 1
- 229940105606 oxycontin Drugs 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 230000008058 pain sensation Effects 0.000 description 1
- WLJNZVDCPSBLRP-UHFFFAOYSA-N pamoic acid Chemical compound C1=CC=C2C(CC=3C4=CC=CC=C4C=C(C=3O)C(=O)O)=C(O)C(C(O)=O)=CC2=C1 WLJNZVDCPSBLRP-UHFFFAOYSA-N 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 229920002866 paraformaldehyde Polymers 0.000 description 1
- 230000001314 paroxysmal effect Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 231100000915 pathological change Toxicity 0.000 description 1
- 230000036285 pathological change Effects 0.000 description 1
- 230000009054 pathological process Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000009984 peri-natal effect Effects 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 230000005043 peripheral vision Effects 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000001050 pharmacotherapy Methods 0.000 description 1
- 125000004934 phenanthridinyl group Chemical group C1(=CC=CC2=NC=C3C=CC=CC3=C12)* 0.000 description 1
- 125000004625 phenanthrolinyl group Chemical group N1=C(C=CC2=CC=C3C=CC=NC3=C12)* 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- 208000019899 phobic disease Diseases 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 208000024335 physical disease Diseases 0.000 description 1
- 230000003863 physical function Effects 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 208000010916 pituitary tumor Diseases 0.000 description 1
- 230000036470 plasma concentration Effects 0.000 description 1
- 229920002401 polyacrylamide Polymers 0.000 description 1
- 108010040003 polyglutamine Proteins 0.000 description 1
- 229920000155 polyglutamine Polymers 0.000 description 1
- 208000005987 polymyositis Diseases 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 150000008442 polyphenolic compounds Chemical class 0.000 description 1
- 235000013824 polyphenols Nutrition 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 208000028173 post-traumatic stress disease Diseases 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 238000004262 preparative liquid chromatography Methods 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 201000009395 primary hyperaldosteronism Diseases 0.000 description 1
- 210000002243 primary neuron Anatomy 0.000 description 1
- 230000000861 pro-apoptotic effect Effects 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 230000026938 proteasomal ubiquitin-dependent protein catabolic process Effects 0.000 description 1
- 208000001381 pseudotumor cerebri Diseases 0.000 description 1
- 230000008433 psychological processes and functions Effects 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000002098 pyridazinyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 150000007660 quinolones Chemical class 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 150000004059 quinone derivatives Chemical class 0.000 description 1
- 125000004151 quinonyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 230000010282 redox signaling Effects 0.000 description 1
- 230000011514 reflex Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000029058 respiratory gaseous exchange Effects 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 230000026416 response to pain Effects 0.000 description 1
- 230000004043 responsiveness Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 239000012266 salt solution Substances 0.000 description 1
- 235000021003 saturated fats Nutrition 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 238000005204 segregation Methods 0.000 description 1
- 201000005572 sensory peripheral neuropathy Diseases 0.000 description 1
- 125000003607 serino group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C(O[H])([H])[H] 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- 208000018316 severe headache Diseases 0.000 description 1
- 230000009528 severe injury Effects 0.000 description 1
- 208000012201 sexual and gender identity disease Diseases 0.000 description 1
- 208000015891 sexual disease Diseases 0.000 description 1
- 239000004208 shellac Substances 0.000 description 1
- ZLGIYFNHBLSMPS-ATJNOEHPSA-N shellac Chemical compound OCCCCCC(O)C(O)CCCCCCCC(O)=O.C1C23[C@H](C(O)=O)CCC2[C@](C)(CO)[C@@H]1C(C(O)=O)=C[C@@H]3O ZLGIYFNHBLSMPS-ATJNOEHPSA-N 0.000 description 1
- 229940113147 shellac Drugs 0.000 description 1
- 235000013874 shellac Nutrition 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 230000007958 sleep Effects 0.000 description 1
- 201000002859 sleep apnea Diseases 0.000 description 1
- 208000019116 sleep disease Diseases 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 210000002460 smooth muscle Anatomy 0.000 description 1
- 239000000344 soap Substances 0.000 description 1
- 210000004872 soft tissue Anatomy 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000007892 solid unit dosage form Substances 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 206010062261 spinal cord neoplasm Diseases 0.000 description 1
- 208000002320 spinal muscular atrophy Diseases 0.000 description 1
- 210000001032 spinal nerve Anatomy 0.000 description 1
- 208000037959 spinal tumor Diseases 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 230000010473 stable expression Effects 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000036262 stenosis Effects 0.000 description 1
- 208000037804 stenosis Diseases 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- 208000023516 stroke disease Diseases 0.000 description 1
- 230000002739 subcortical effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000001384 succinic acid Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003462 sulfoxides Chemical class 0.000 description 1
- 125000004434 sulfur atom Chemical group 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000009747 swallowing Effects 0.000 description 1
- 229940127230 sympathomimetic drug Drugs 0.000 description 1
- 239000011885 synergistic combination Substances 0.000 description 1
- 229920001059 synthetic polymer Polymers 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 208000009056 telangiectasis Diseases 0.000 description 1
- 208000001189 temporomandibular joint dysfunction syndrome Diseases 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 201000006361 tethered spinal cord syndrome Diseases 0.000 description 1
- 125000001712 tetrahydronaphthyl group Chemical group C1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000004853 tetrahydropyridinyl group Chemical group N1(CCCC=C1)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 125000002813 thiocarbonyl group Chemical group *C(*)=S 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- 229940094937 thioredoxin Drugs 0.000 description 1
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 210000003371 toe Anatomy 0.000 description 1
- 238000011200 topical administration Methods 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- 230000009261 transgenic effect Effects 0.000 description 1
- 201000010875 transient cerebral ischemia Diseases 0.000 description 1
- 238000003146 transient transfection Methods 0.000 description 1
- 208000009174 transverse myelitis Diseases 0.000 description 1
- 230000009529 traumatic brain injury Effects 0.000 description 1
- 229960002622 triacetin Drugs 0.000 description 1
- 125000001425 triazolyl group Chemical group 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 206010044652 trigeminal neuralgia Diseases 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- 125000005423 trihalomethanesulfonamido group Chemical group 0.000 description 1
- 125000005152 trihalomethanesulfonyl group Chemical group 0.000 description 1
- 125000004951 trihalomethoxy group Chemical group 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003648 triterpenes Chemical class 0.000 description 1
- 208000006961 tropical spastic paraparesis Diseases 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 238000010798 ubiquitination Methods 0.000 description 1
- 230000034512 ubiquitination Effects 0.000 description 1
- WTMFRMMLJJWJRG-UHFFFAOYSA-N undeca-2,6-diene Chemical compound CCCCC=CCCC=CC WTMFRMMLJJWJRG-UHFFFAOYSA-N 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000002700 urine Anatomy 0.000 description 1
- 238000001291 vacuum drying Methods 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 230000009385 viral infection Effects 0.000 description 1
- 230000021542 voluntary musculoskeletal movement Effects 0.000 description 1
- 208000006542 von Hippel-Lindau disease Diseases 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 210000004885 white matter Anatomy 0.000 description 1
- 239000009637 wintergreen oil Substances 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/32—Unsaturated compounds containing hydroxy or O-metal groups
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/06—Antimigraine agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/08—Antiepileptics; Anticonvulsants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C62/00—Compounds having carboxyl groups bound to carbon atoms of rings other than six—membered aromatic rings and containing any of the groups OH, O—metal, —CHO, keto, ether, groups, groups, or groups
- C07C62/30—Unsaturated compounds
- C07C62/38—Unsaturated compounds containing keto groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/74—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring
- C07C69/757—Esters of carboxylic acids having an esterified carboxyl group bound to a carbon atom of a ring other than a six-membered aromatic ring having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/14—All rings being cycloaliphatic
- C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Pain & Pain Management (AREA)
- Psychiatry (AREA)
- Ophthalmology & Optometry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Psychology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US85086006P | 2006-10-10 | 2006-10-10 | |
| US85091806P | 2006-10-10 | 2006-10-10 | |
| PCT/US2007/021748 WO2008108825A2 (en) | 2006-10-10 | 2007-10-10 | Neuroprotective compositions and methods |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2010505958A true JP2010505958A (ja) | 2010-02-25 |
| JP2010505958A5 JP2010505958A5 (OSRAM) | 2010-11-25 |
Family
ID=39738942
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2009532414A Pending JP2010505958A (ja) | 2006-10-10 | 2007-10-10 | 神経防護作用組成物および方法 |
Country Status (5)
| Country | Link |
|---|---|
| US (2) | US8022246B2 (OSRAM) |
| EP (1) | EP2086318A4 (OSRAM) |
| JP (1) | JP2010505958A (OSRAM) |
| CA (1) | CA2666461A1 (OSRAM) |
| WO (1) | WO2008108825A2 (OSRAM) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015519873A (ja) * | 2012-03-30 | 2015-07-16 | ネステク ソシエテ アノニム | ４−オキソ−２−ペンテン酸及び脳の健康 |
| JP2016511282A (ja) * | 2013-03-14 | 2016-04-14 | ユニバーシティ オブ マカオＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｃａｕ | ヤクチ（益智（ａｌｐｉｎｉａｅｏｘｙｐｈｙｌｌａｅｆｒｕｃｔｕｓ））およびその全合成から単離される新規な抗神経変性天然化合物 |
Families Citing this family (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2142182B1 (en) | 2007-02-06 | 2017-09-27 | Neuroquest Inc. | Composition comprising terpene compounds and methods for inhibiting nerve transmission |
| WO2010017626A1 (en) | 2008-08-13 | 2010-02-18 | Origin Biomed Inc. | Compositions comprising terpene compounds for treating negative sensory phenomena |
| EP3827815B1 (en) | 2008-09-10 | 2023-09-06 | PTC Therapeutics, Inc. | Treatment of pervasive developmental disorders with redox-active therapeutics |
| GB2464813A (en) * | 2009-10-23 | 2010-05-05 | Univ Sheffield | Treatments for neurodegenerative disorders |
| US20130102477A1 (en) | 2010-06-23 | 2013-04-25 | Ryan D. Morin | Biomarkers for non-hodgkin lymphomas and uses thereof |
| RU2618475C2 (ru) | 2010-09-10 | 2017-05-03 | Эпизайм, Инк. | Ингибиторы ezh2 человека и способы их применения |
| US9175331B2 (en) | 2010-09-10 | 2015-11-03 | Epizyme, Inc. | Inhibitors of human EZH2, and methods of use thereof |
| CA2811241A1 (en) * | 2010-09-14 | 2012-03-22 | Neuroquest Inc. | Terpenoid analogues and uses thereof for treating neurological conditions |
| WO2012094580A2 (en) * | 2011-01-07 | 2012-07-12 | High Point Pharmaceuticals, Llc | Compounds that modulate oxidative stress |
| TW201733984A (zh) | 2011-04-13 | 2017-10-01 | 雅酶股份有限公司 | 經取代之苯化合物 |
| JO3438B1 (ar) | 2011-04-13 | 2019-10-20 | Epizyme Inc | مركبات بنزين مستبدلة بأريل أو أريل غير متجانس |
| US20140256767A1 (en) * | 2011-10-31 | 2014-09-11 | The Broad Institute, Inc. | Direct inhibitors of keap1-nrf2 interaction as antioxidant inflammation modulators |
| LT2836491T (lt) | 2012-04-13 | 2017-03-27 | Epizyme, Inc. | Žmogaus histono metiltransferazės ezh2 slopiklio druskos forma |
| CN105102431B (zh) | 2012-10-15 | 2018-03-02 | Epizyme股份有限公司 | 经取代的苯化合物 |
| EP2931292B1 (en) | 2012-12-13 | 2018-06-13 | Warsaw Orthopedic, Inc. | Compositions and methods comprising polyethylene glycol and magnesium for treatment of neuronal injury |
| CA2925889C (en) | 2013-10-16 | 2020-09-29 | Epizyme, Inc. | Hydrochloride salt form for ezh2 inhibition |
| WO2016173274A1 (zh) | 2015-04-30 | 2016-11-03 | 中国科学院微生物研究所 | 芳香族法尼基类化合物及其应用 |
| US10123991B2 (en) | 2015-05-15 | 2018-11-13 | Global Biolife Inc. | Electrophilically enhanced phenolic compounds for treating inflammatory related diseases and disorders |
| EP3106160B8 (en) | 2015-06-15 | 2019-12-11 | Neuralia | Combination composition comprising huperzine |
| US10703701B2 (en) | 2015-12-17 | 2020-07-07 | Ptc Therapeutics, Inc. | Fluoroalkyl, fluoroalkoxy, phenoxy, heteroaryloxy, alkoxy, and amine 1,4-benzoquinone derivatives for treatment of oxidative stress disorders |
| ES2974026T3 (es) | 2018-08-20 | 2024-06-25 | Janssen Pharmaceutica Nv | Inhibidores de la interacción proteína-proteína entre KEAP1-Nrf2 |
| CN111166885B (zh) * | 2020-01-16 | 2022-03-15 | 上海交通大学医学院 | 神经保护剂及其用途 |
| CN114588143B (zh) * | 2020-12-03 | 2023-06-06 | 中国科学院大连化学物理研究所 | 药物组合物及化合物作为或在制备阿片受体拮抗剂中的应用 |
| WO2023055733A1 (en) * | 2021-09-30 | 2023-04-06 | The Scripps Research Institute | Compounds for reducing neuroinflammation |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010034370A1 (en) * | 2000-02-28 | 2001-10-25 | Kunio Kosaka | Carnosic acid derivatives for promoting synthesis of nerve growth factor |
| JP2009515821A (ja) * | 2005-10-16 | 2009-04-16 | リコレッド リミテッド | 眼疾患を治療するための組成物 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3976782A (en) * | 1975-03-25 | 1976-08-24 | Merck & Co., Inc. | 3-(2,5-Dihydroxyphenyl)-alanine as a cardiac stimulant |
| US4938949A (en) | 1988-09-12 | 1990-07-03 | University Of New York | Treatment of damaged bone marrow and dosage units therefor |
| EP0472733B1 (en) | 1990-03-06 | 1994-12-28 | Otsuka Pharmaceutical Co., Ltd. | Phenanthrene derivative |
| DE69012566T2 (de) | 1990-10-06 | 1995-02-02 | Nestle Sa | Verfahren zur Gewinnung von Carnosäure. |
| AU703958B2 (en) | 1995-05-05 | 1999-04-01 | Hauser Inc. | High purity carnosic acid from rosemary and sage extracts by PH-controlled precipitation |
| CA2286801C (en) | 1997-04-16 | 2006-03-14 | Lycored Natural Products Industries Ltd. | A novel process to produce stabilized carnosic acid in high concentration |
| AU2001271824A1 (en) * | 2000-07-05 | 2002-01-14 | Johns Hopkins School Of Medicine | Prevention and treatment of neurodegenerative diseases by glutathione and phase ii detoxification enzymes |
| US20040014808A1 (en) | 2002-04-09 | 2004-01-22 | Rosazza John P.N. | Novel derivatives of carnosic acid |
| GB0216371D0 (en) | 2002-07-13 | 2002-08-21 | Rowett Res Inst The | Compounds |
| US7129374B2 (en) | 2002-11-26 | 2006-10-31 | Florida Atlantic University | Catalytic antioxidants and methods of use |
| US20040224995A1 (en) * | 2003-05-09 | 2004-11-11 | University Of North Texas Health Science Center At Fort Worth | Neuroprotective effects of PPARy agonists against cellular oxidative insults |
| CN1897972A (zh) | 2003-12-22 | 2007-01-17 | 爱尔康公司 | 用于治疗青光眼性视网膜病和视神经病的活性剂 |
-
2007
- 2007-10-10 WO PCT/US2007/021748 patent/WO2008108825A2/en not_active Ceased
- 2007-10-10 EP EP07873874A patent/EP2086318A4/en not_active Withdrawn
- 2007-10-10 CA CA002666461A patent/CA2666461A1/en not_active Abandoned
- 2007-10-10 US US11/974,114 patent/US8022246B2/en not_active Expired - Fee Related
- 2007-10-10 JP JP2009532414A patent/JP2010505958A/ja active Pending
-
2011
- 2011-09-19 US US13/236,579 patent/US8466311B2/en not_active Expired - Fee Related
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20010034370A1 (en) * | 2000-02-28 | 2001-10-25 | Kunio Kosaka | Carnosic acid derivatives for promoting synthesis of nerve growth factor |
| JP2009515821A (ja) * | 2005-10-16 | 2009-04-16 | リコレッド リミテッド | 眼疾患を治療するための組成物 |
Non-Patent Citations (2)
| Title |
|---|
| JPN6012065742; Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｂｉｏｌｏｇｉｃａｌ Ｃｈｅｍｉｓｔｒｙ ２７９（１０）, 2004, ｐ．８９１９-８９２９ * |
| JPN7012005166; Ｂｉｏｌ．Ｐｈａｒｍ．Ｂｕｌｌ． ２６（１１）, 2003, ｐ．１６２０-１６２２ * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2015519873A (ja) * | 2012-03-30 | 2015-07-16 | ネステク ソシエテ アノニム | ４−オキソ−２−ペンテン酸及び脳の健康 |
| JP2016511282A (ja) * | 2013-03-14 | 2016-04-14 | ユニバーシティ オブ マカオＵｎｉｖｅｒｓｉｔｙ Ｏｆ Ｍａｃａｕ | ヤクチ（益智（ａｌｐｉｎｉａｅｏｘｙｐｈｙｌｌａｅｆｒｕｃｔｕｓ））およびその全合成から単離される新規な抗神経変性天然化合物 |
| US10011555B2 (en) | 2013-03-14 | 2018-07-03 | University Of Macau | Methods of treating Parkinson's disease |
Also Published As
| Publication number | Publication date |
|---|---|
| US20090042980A1 (en) | 2009-02-12 |
| US20120296112A1 (en) | 2012-11-22 |
| WO2008108825A2 (en) | 2008-09-12 |
| EP2086318A2 (en) | 2009-08-12 |
| EP2086318A4 (en) | 2009-12-23 |
| CA2666461A1 (en) | 2008-09-12 |
| US8022246B2 (en) | 2011-09-20 |
| WO2008108825A3 (en) | 2008-12-18 |
| US8466311B2 (en) | 2013-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US8466311B2 (en) | Neuroprotective compositions and methods | |
| US20190000867A1 (en) | Compounds, compositions and methods for protecting brain health in neurodegenerative disorders | |
| JP6563193B2 (ja) | Ｄｃｐｌａのエステル、およびそれを用いた処置の方法 | |
| AU2021269396B2 (en) | Very-long-chain polyunsaturated fatty acids, elovanoid hydroxylated derivatives, and methods of use | |
| CN102946877B (zh) | 乳突果及其分离的化合物在制备用于治疗神经疾病的药物中的用途 | |
| EP2720693B1 (en) | Chromane-like cyclic prenylflavonoids for the medical intervention in neurological disorders | |
| Lin et al. | 3, 6’-dithiopomalidomide reduces neural loss, inflammation, behavioral deficits in brain injury and microglial activation | |
| US20230404990A1 (en) | Neuroprotective cb2 receptor agonists | |
| US20210023048A1 (en) | Dosing regimens of pkc activators | |
| WO2004092179A1 (ja) | スピロ誘導体、製造法および抗酸化薬 | |
| EP4452939A1 (en) | Polypodal serotonergic compounds and prodrugs of serotonin receptor agonists and antagonists | |
| JP2008531558A (ja) | 新規なリポオキシゲナーゼ阻害剤 | |
| WO2023023298A1 (en) | Hallucinogenic and non-hallucinogenic compounds and methods of making and using the same | |
| JP2012529477A (ja) | ５’−メチルチオアデノシンの神経保護特性 | |
| CN117136050A (zh) | 用于使用大麻素治疗神经元病症的组合物和方法 | |
| JP2008517901A (ja) | 経口で有効なカンナビノイド類似体 | |
| JP2023501151A (ja) | 神経変性疾患及び／又はその臨床的状態を抑制及び／又は治療するための組成物及び方法 | |
| CA2961630A1 (en) | C-20 steroid compounds, compositions and uses thereof to treat traumatic brain injury (tbi), including concussions | |
| CA3086945A1 (en) | Variants of 2-[6-(4-chlorophenoxy)hexyl]-oxirane-2-carboxylic acid for use in the treatment, prevention and/or amelioration of brain diseases | |
| KR20250155546A (ko) | 파킨슨병의 치료에 있어서의 메트포르민과 글리벤클라미드의 병용 | |
| KR20240073178A (ko) | 부채마 추출물 또는 디오신을 포함하는 기억력 개선, 신경염증 억제, 신경세포 사멸 억제, 또는 자가포식작용 촉진용 조성물 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20101007 |
|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20101007 |
|
| RD03 | Notification of appointment of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7423 Effective date: 20101007 |
|
| RD04 | Notification of resignation of power of attorney |
Free format text: JAPANESE INTERMEDIATE CODE: A7424 Effective date: 20101007 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20121211 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20121218 |
|
| A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20130521 |