CA2615129A1 - Carbamate compounds for use in treating neurodegenerative disorders - Google Patents
Carbamate compounds for use in treating neurodegenerative disorders Download PDFInfo
- Publication number
- CA2615129A1 CA2615129A1 CA002615129A CA2615129A CA2615129A1 CA 2615129 A1 CA2615129 A1 CA 2615129A1 CA 002615129 A CA002615129 A CA 002615129A CA 2615129 A CA2615129 A CA 2615129A CA 2615129 A1 CA2615129 A1 CA 2615129A1
- Authority
- CA
- Canada
- Prior art keywords
- formula
- group
- enantiomer
- rats
- phenyl
- 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.)
- Abandoned
Links
- 208000015122 neurodegenerative disease Diseases 0.000 title claims description 13
- 150000004657 carbamic acid derivatives Chemical class 0.000 title description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 124
- 238000000034 method Methods 0.000 claims abstract description 89
- 230000004112 neuroprotection Effects 0.000 claims abstract description 50
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 27
- 150000003839 salts Chemical class 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 22
- 239000001257 hydrogen Substances 0.000 claims abstract description 21
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 21
- 239000000460 chlorine Substances 0.000 claims abstract description 19
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract description 18
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 17
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 14
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims abstract description 11
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 11
- 239000011737 fluorine Substances 0.000 claims abstract description 11
- 229910052731 fluorine Inorganic materials 0.000 claims abstract description 11
- 239000011630 iodine Substances 0.000 claims abstract description 11
- 229910052740 iodine Inorganic materials 0.000 claims abstract description 11
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims abstract description 10
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 7
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 7
- 150000002367 halogens Chemical group 0.000 claims abstract description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 7
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract 5
- 206010010904 Convulsion Diseases 0.000 claims description 103
- 208000005809 status epilepticus Diseases 0.000 claims description 72
- 238000011282 treatment Methods 0.000 claims description 60
- 230000006378 damage Effects 0.000 claims description 57
- 208000014674 injury Diseases 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 54
- 239000003814 drug Substances 0.000 claims description 46
- 230000000694 effects Effects 0.000 claims description 41
- 208000027418 Wounds and injury Diseases 0.000 claims description 37
- 229940079593 drug Drugs 0.000 claims description 31
- 230000000324 neuroprotective effect Effects 0.000 claims description 27
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 26
- -1 lamotigine Chemical compound 0.000 claims description 26
- 230000003961 neuronal insult Effects 0.000 claims description 25
- 230000001537 neural effect Effects 0.000 claims description 24
- 210000003169 central nervous system Anatomy 0.000 claims description 21
- 206010015037 epilepsy Diseases 0.000 claims description 20
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 230000008733 trauma Effects 0.000 claims description 18
- 208000035475 disorder Diseases 0.000 claims description 15
- 230000004770 neurodegeneration Effects 0.000 claims description 15
- 208000030886 Traumatic Brain injury Diseases 0.000 claims description 13
- 210000002966 serum Anatomy 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 12
- 208000024827 Alzheimer disease Diseases 0.000 claims description 11
- 208000006011 Stroke Diseases 0.000 claims description 11
- 229940124597 therapeutic agent Drugs 0.000 claims description 11
- 230000009529 traumatic brain injury Effects 0.000 claims description 11
- 231100000331 toxic Toxicity 0.000 claims description 10
- 230000002588 toxic effect Effects 0.000 claims description 10
- 239000001961 anticonvulsive agent Substances 0.000 claims description 9
- 208000028867 ischemia Diseases 0.000 claims description 9
- 208000024891 symptom Diseases 0.000 claims description 9
- 230000001225 therapeutic effect Effects 0.000 claims description 9
- 239000000090 biomarker Substances 0.000 claims description 8
- 206010021143 Hypoxia Diseases 0.000 claims description 7
- 229960003965 antiepileptics Drugs 0.000 claims description 7
- 239000002552 dosage form Substances 0.000 claims description 7
- 238000002595 magnetic resonance imaging Methods 0.000 claims description 7
- 208000023105 Huntington disease Diseases 0.000 claims description 6
- 238000001356 surgical procedure Methods 0.000 claims description 6
- 208000018737 Parkinson disease Diseases 0.000 claims description 5
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 5
- 206010012601 diabetes mellitus Diseases 0.000 claims description 5
- 230000004064 dysfunction Effects 0.000 claims description 5
- 230000005764 inhibitory process Effects 0.000 claims description 5
- 230000003902 lesion Effects 0.000 claims description 5
- 201000006417 multiple sclerosis Diseases 0.000 claims description 5
- 230000007170 pathology Effects 0.000 claims description 5
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 claims description 4
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 claims description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 4
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 claims description 4
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 claims description 4
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 claims description 4
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 claims description 4
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 claims description 4
- 208000028361 Penetrating Head injury Diseases 0.000 claims description 4
- 201000007737 Retinal degeneration Diseases 0.000 claims description 4
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 claims description 4
- 239000011575 calcium Substances 0.000 claims description 4
- 208000026106 cerebrovascular disease Diseases 0.000 claims description 4
- 239000002738 chelating agent Substances 0.000 claims description 4
- 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 claims description 4
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 4
- 239000003112 inhibitor Substances 0.000 claims description 4
- 230000004258 retinal degeneration Effects 0.000 claims description 4
- 208000018652 Closed Head injury Diseases 0.000 claims description 3
- 208000010859 Creutzfeldt-Jakob disease Diseases 0.000 claims description 3
- 208000010412 Glaucoma Diseases 0.000 claims description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 3
- 208000001089 Multiple system atrophy Diseases 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 208000024777 Prion disease Diseases 0.000 claims description 3
- 206010044245 Toxic optic neuropathy Diseases 0.000 claims description 3
- 230000003078 antioxidant effect Effects 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- 229960001233 pregabalin Drugs 0.000 claims description 3
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 claims description 3
- 208000032253 retinal ischemia Diseases 0.000 claims description 3
- 230000004799 sedative–hypnotic effect Effects 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 208000011117 substance-related disease Diseases 0.000 claims description 3
- 206010002660 Anoxia Diseases 0.000 claims description 2
- 241000976983 Anoxia Species 0.000 claims description 2
- 208000003174 Brain Neoplasms Diseases 0.000 claims description 2
- 206010048962 Brain oedema Diseases 0.000 claims description 2
- 108090000312 Calcium Channels Proteins 0.000 claims description 2
- 102000003922 Calcium Channels Human genes 0.000 claims description 2
- 108010045403 Calcium-Binding Proteins Proteins 0.000 claims description 2
- 102000005701 Calcium-Binding Proteins Human genes 0.000 claims description 2
- 206010008111 Cerebral haemorrhage Diseases 0.000 claims description 2
- 108010062745 Chloride Channels Proteins 0.000 claims description 2
- 102000011045 Chloride Channels Human genes 0.000 claims description 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims description 2
- 208000002091 Febrile Seizures Diseases 0.000 claims description 2
- 208000010496 Heart Arrest Diseases 0.000 claims description 2
- 108010035210 Iron-Binding Proteins Proteins 0.000 claims description 2
- 102000008133 Iron-Binding Proteins Human genes 0.000 claims description 2
- 102000008299 Nitric Oxide Synthase Human genes 0.000 claims description 2
- 108010021487 Nitric Oxide Synthase Proteins 0.000 claims description 2
- CXOFVDLJLONNDW-UHFFFAOYSA-N Phenytoin Chemical compound N1C(=O)NC(=O)C1(C=1C=CC=CC=1)C1=CC=CC=C1 CXOFVDLJLONNDW-UHFFFAOYSA-N 0.000 claims description 2
- 102000004257 Potassium Channel Human genes 0.000 claims description 2
- 108010052164 Sodium Channels Proteins 0.000 claims description 2
- 102000018674 Sodium Channels Human genes 0.000 claims description 2
- 208000002667 Subdural Hematoma Diseases 0.000 claims description 2
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 claims description 2
- 231100000643 Substance intoxication Toxicity 0.000 claims description 2
- JACAAXNEHGBPOQ-LLVKDONJSA-N Talampanel Chemical compound C([C@H](N(N=1)C(C)=O)C)C2=CC=3OCOC=3C=C2C=1C1=CC=C(N)C=C1 JACAAXNEHGBPOQ-LLVKDONJSA-N 0.000 claims description 2
- KJADKKWYZYXHBB-XBWDGYHZSA-N Topiramic acid Chemical compound C1O[C@@]2(COS(N)(=O)=O)OC(C)(C)O[C@H]2[C@@H]2OC(C)(C)O[C@@H]21 KJADKKWYZYXHBB-XBWDGYHZSA-N 0.000 claims description 2
- 206010070863 Toxicity to various agents Diseases 0.000 claims description 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 2
- 230000007953 anoxia Effects 0.000 claims description 2
- 229940125717 barbiturate Drugs 0.000 claims description 2
- 229940049706 benzodiazepine Drugs 0.000 claims description 2
- 150000001557 benzodiazepines Chemical class 0.000 claims description 2
- 208000006752 brain edema Diseases 0.000 claims description 2
- 229960000623 carbamazepine Drugs 0.000 claims description 2
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 claims description 2
- OEUUFNIKLCFNLN-LLVKDONJSA-N chembl432481 Chemical compound OC(=O)[C@@]1(C)CSC(C=2C(=CC(O)=CC=2)O)=N1 OEUUFNIKLCFNLN-LLVKDONJSA-N 0.000 claims description 2
- CXOXHMZGEKVPMT-UHFFFAOYSA-N clobazam Chemical compound O=C1CC(=O)N(C)C2=CC=C(Cl)C=C2N1C1=CC=CC=C1 CXOXHMZGEKVPMT-UHFFFAOYSA-N 0.000 claims description 2
- 229960001403 clobazam Drugs 0.000 claims description 2
- DGBIGWXXNGSACT-UHFFFAOYSA-N clonazepam Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(=O)CN=C1C1=CC=CC=C1Cl DGBIGWXXNGSACT-UHFFFAOYSA-N 0.000 claims description 2
- 229960003120 clonazepam Drugs 0.000 claims description 2
- 229960003920 cocaine Drugs 0.000 claims description 2
- 239000007857 degradation product Substances 0.000 claims description 2
- 229960002767 ethosuximide Drugs 0.000 claims description 2
- HAPOVYFOVVWLRS-UHFFFAOYSA-N ethosuximide Chemical compound CCC1(C)CC(=O)NC1=O HAPOVYFOVVWLRS-UHFFFAOYSA-N 0.000 claims description 2
- PCOBBVZJEWWZFR-UHFFFAOYSA-N ezogabine Chemical compound C1=C(N)C(NC(=O)OCC)=CC=C1NCC1=CC=C(F)C=C1 PCOBBVZJEWWZFR-UHFFFAOYSA-N 0.000 claims description 2
- 229960003472 felbamate Drugs 0.000 claims description 2
- WKGXYQFOCVYPAC-UHFFFAOYSA-N felbamate Chemical compound NC(=O)OCC(COC(N)=O)C1=CC=CC=C1 WKGXYQFOCVYPAC-UHFFFAOYSA-N 0.000 claims description 2
- 229960002870 gabapentin Drugs 0.000 claims description 2
- 229960004002 levetiracetam Drugs 0.000 claims description 2
- HPHUVLMMVZITSG-ZCFIWIBFSA-N levetiracetam Chemical compound CC[C@H](C(N)=O)N1CCCC1=O HPHUVLMMVZITSG-ZCFIWIBFSA-N 0.000 claims description 2
- 208000002780 macular degeneration Diseases 0.000 claims description 2
- 208000030159 metabolic disease Diseases 0.000 claims description 2
- 208000031237 olivopontocerebellar atrophy Diseases 0.000 claims description 2
- 229960001816 oxcarbazepine Drugs 0.000 claims description 2
- CTRLABGOLIVAIY-UHFFFAOYSA-N oxcarbazepine Chemical compound C1C(=O)C2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 CTRLABGOLIVAIY-UHFFFAOYSA-N 0.000 claims description 2
- 229960002695 phenobarbital Drugs 0.000 claims description 2
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 claims description 2
- 229960002036 phenytoin Drugs 0.000 claims description 2
- 108020001213 potassium channel Proteins 0.000 claims description 2
- 229960002393 primidone Drugs 0.000 claims description 2
- DQMZLTXERSFNPB-UHFFFAOYSA-N primidone Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NCNC1=O DQMZLTXERSFNPB-UHFFFAOYSA-N 0.000 claims description 2
- 229960003312 retigabine Drugs 0.000 claims description 2
- AEQFSUDEHCCHBT-UHFFFAOYSA-M sodium valproate Chemical compound [Na+].CCCC(C([O-])=O)CCC AEQFSUDEHCCHBT-UHFFFAOYSA-M 0.000 claims description 2
- 210000000278 spinal cord Anatomy 0.000 claims description 2
- 201000009032 substance abuse Diseases 0.000 claims description 2
- 231100000736 substance abuse Toxicity 0.000 claims description 2
- 238000011477 surgical intervention Methods 0.000 claims description 2
- 229950004608 talampanel Drugs 0.000 claims description 2
- PBJUNZJWGZTSKL-MRXNPFEDSA-N tiagabine Chemical compound C1=CSC(C(=CCCN2C[C@@H](CCC2)C(O)=O)C2=C(C=CS2)C)=C1C PBJUNZJWGZTSKL-MRXNPFEDSA-N 0.000 claims description 2
- 229960001918 tiagabine Drugs 0.000 claims description 2
- 229960004394 topiramate Drugs 0.000 claims description 2
- 229940102566 valproate Drugs 0.000 claims description 2
- 229960005318 vigabatrin Drugs 0.000 claims description 2
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 claims description 2
- 230000004572 zinc-binding Effects 0.000 claims description 2
- 229960002911 zonisamide Drugs 0.000 claims description 2
- UBQNRHZMVUUOMG-UHFFFAOYSA-N zonisamide Chemical compound C1=CC=C2C(CS(=O)(=O)N)=NOC2=C1 UBQNRHZMVUUOMG-UHFFFAOYSA-N 0.000 claims description 2
- 125000001309 chloro group Chemical group Cl* 0.000 claims 3
- 208000032843 Hemorrhage Diseases 0.000 claims 2
- 238000009877 rendering Methods 0.000 claims 2
- 208000023275 Autoimmune disease Diseases 0.000 claims 1
- 208000034826 Genetic Predisposition to Disease Diseases 0.000 claims 1
- 206010020843 Hyperthermia Diseases 0.000 claims 1
- 208000013016 Hypoglycemia Diseases 0.000 claims 1
- 206010058558 Hypoperfusion Diseases 0.000 claims 1
- 208000001953 Hypotension Diseases 0.000 claims 1
- 206010028923 Neonatal asphyxia Diseases 0.000 claims 1
- 208000037212 Neonatal hypoxic and ischemic brain injury Diseases 0.000 claims 1
- 230000008485 antagonism Effects 0.000 claims 1
- 208000034158 bleeding Diseases 0.000 claims 1
- 230000000740 bleeding effect Effects 0.000 claims 1
- 238000013172 carotid endarterectomy Methods 0.000 claims 1
- 238000002585 cerebral angiography Methods 0.000 claims 1
- 208000005017 glioblastoma Diseases 0.000 claims 1
- 230000036031 hyperthermia Effects 0.000 claims 1
- 230000002218 hypoglycaemic effect Effects 0.000 claims 1
- 230000036543 hypotension Effects 0.000 claims 1
- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 238000002250 neutron powder diffraction Methods 0.000 claims 1
- 208000033300 perinatal asphyxia Diseases 0.000 claims 1
- 231100000614 poison Toxicity 0.000 claims 1
- 230000007096 poisonous effect Effects 0.000 claims 1
- 230000002792 vascular Effects 0.000 claims 1
- 125000000217 alkyl group Chemical group 0.000 abstract description 6
- 241000700159 Rattus Species 0.000 description 137
- 241001465754 Metazoa Species 0.000 description 58
- 210000004027 cell Anatomy 0.000 description 58
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 43
- 238000012360 testing method Methods 0.000 description 42
- 229960003529 diazepam Drugs 0.000 description 37
- 210000002569 neuron Anatomy 0.000 description 36
- 229960001416 pilocarpine Drugs 0.000 description 33
- 210000001320 hippocampus Anatomy 0.000 description 27
- 235000002639 sodium chloride Nutrition 0.000 description 27
- 238000002347 injection Methods 0.000 description 24
- 239000007924 injection Substances 0.000 description 24
- 230000002269 spontaneous effect Effects 0.000 description 22
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 20
- 238000009472 formulation Methods 0.000 description 20
- 229930195712 glutamate Natural products 0.000 description 20
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 19
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 19
- 210000004556 brain Anatomy 0.000 description 18
- 239000011780 sodium chloride Substances 0.000 description 17
- 210000001353 entorhinal cortex Anatomy 0.000 description 16
- 230000001965 increasing effect Effects 0.000 description 16
- 230000006727 cell loss Effects 0.000 description 15
- 230000008579 epileptogenesis Effects 0.000 description 15
- 210000000653 nervous system Anatomy 0.000 description 15
- 230000001037 epileptic effect Effects 0.000 description 14
- 210000004940 nucleus Anatomy 0.000 description 14
- 210000001103 thalamus Anatomy 0.000 description 13
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 12
- 230000001154 acute effect Effects 0.000 description 12
- 239000000243 solution Substances 0.000 description 12
- 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 11
- 239000000546 pharmaceutical excipient Substances 0.000 description 11
- 230000000306 recurrent effect Effects 0.000 description 11
- 230000002829 reductive effect Effects 0.000 description 11
- 241000282414 Homo sapiens Species 0.000 description 10
- 210000004727 amygdala Anatomy 0.000 description 10
- 230000001684 chronic effect Effects 0.000 description 10
- 201000010099 disease Diseases 0.000 description 10
- 230000003492 excitotoxic effect Effects 0.000 description 10
- 239000008187 granular material Substances 0.000 description 10
- 238000007912 intraperitoneal administration Methods 0.000 description 10
- 201000008914 temporal lobe epilepsy Diseases 0.000 description 10
- 230000007850 degeneration Effects 0.000 description 9
- 231100000063 excitotoxicity Toxicity 0.000 description 9
- 230000000750 progressive effect Effects 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 8
- 230000003247 decreasing effect Effects 0.000 description 8
- 210000001947 dentate gyrus Anatomy 0.000 description 8
- 239000003826 tablet Substances 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- 229930006000 Sucrose Natural products 0.000 description 7
- 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 7
- 238000011161 development Methods 0.000 description 7
- 230000018109 developmental process Effects 0.000 description 7
- 239000006196 drop Substances 0.000 description 7
- 230000016273 neuron death Effects 0.000 description 7
- 210000001428 peripheral nervous system Anatomy 0.000 description 7
- 239000005720 sucrose Substances 0.000 description 7
- 230000004083 survival effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 206010012289 Dementia Diseases 0.000 description 6
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 238000003556 assay Methods 0.000 description 6
- 230000003542 behavioural effect Effects 0.000 description 6
- 230000008901 benefit Effects 0.000 description 6
- 231100000433 cytotoxic Toxicity 0.000 description 6
- 230000001472 cytotoxic effect Effects 0.000 description 6
- 239000000839 emulsion Substances 0.000 description 6
- 230000002093 peripheral effect Effects 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 6
- 238000011002 quantification Methods 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 238000007920 subcutaneous administration Methods 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 108010010803 Gelatin Proteins 0.000 description 5
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 5
- 206010063629 Hippocampal sclerosis Diseases 0.000 description 5
- 241000124008 Mammalia Species 0.000 description 5
- 208000001738 Nervous System Trauma Diseases 0.000 description 5
- 230000009692 acute damage Effects 0.000 description 5
- 239000000443 aerosol Substances 0.000 description 5
- 239000000969 carrier Substances 0.000 description 5
- 230000030833 cell death Effects 0.000 description 5
- 230000002490 cerebral effect Effects 0.000 description 5
- 239000007859 condensation product Substances 0.000 description 5
- 235000014113 dietary fatty acids Nutrition 0.000 description 5
- 239000000194 fatty acid Substances 0.000 description 5
- 229930195729 fatty acid Natural products 0.000 description 5
- 150000004665 fatty acids Chemical class 0.000 description 5
- 229920000159 gelatin Polymers 0.000 description 5
- 239000008273 gelatin Substances 0.000 description 5
- 235000019322 gelatine Nutrition 0.000 description 5
- 235000011852 gelatine desserts Nutrition 0.000 description 5
- 239000007788 liquid Substances 0.000 description 5
- 210000001073 mediodorsal thalamic nucleus Anatomy 0.000 description 5
- 239000004005 microsphere Substances 0.000 description 5
- 230000004224 protection Effects 0.000 description 5
- 210000002763 pyramidal cell Anatomy 0.000 description 5
- 238000010186 staining Methods 0.000 description 5
- 238000007619 statistical method Methods 0.000 description 5
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 4
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 4
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 4
- 208000028017 Psychotic disease Diseases 0.000 description 4
- 230000002059 anti-epileptogenic effect Effects 0.000 description 4
- 239000007900 aqueous suspension Substances 0.000 description 4
- 230000027455 binding Effects 0.000 description 4
- 210000004369 blood Anatomy 0.000 description 4
- 210000003710 cerebral cortex Anatomy 0.000 description 4
- 206010008118 cerebral infarction Diseases 0.000 description 4
- 238000002591 computed tomography Methods 0.000 description 4
- 230000001054 cortical effect Effects 0.000 description 4
- 230000034994 death Effects 0.000 description 4
- 230000007423 decrease Effects 0.000 description 4
- 230000002461 excitatory amino acid Effects 0.000 description 4
- 239000003257 excitatory amino acid Substances 0.000 description 4
- 239000000796 flavoring agent Substances 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 210000003128 head Anatomy 0.000 description 4
- 230000000971 hippocampal effect Effects 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 239000002502 liposome Substances 0.000 description 4
- 229910052744 lithium Inorganic materials 0.000 description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 4
- 230000007774 longterm Effects 0.000 description 4
- 238000002483 medication Methods 0.000 description 4
- 201000001119 neuropathy Diseases 0.000 description 4
- 230000007823 neuropathy Effects 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 230000036961 partial effect Effects 0.000 description 4
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 4
- 239000003755 preservative agent Substances 0.000 description 4
- 230000001681 protective effect Effects 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 239000000600 sorbitol Substances 0.000 description 4
- 235000010356 sorbitol Nutrition 0.000 description 4
- 239000003053 toxin Substances 0.000 description 4
- 231100000765 toxin Toxicity 0.000 description 4
- 108700012359 toxins Proteins 0.000 description 4
- 238000011269 treatment regimen Methods 0.000 description 4
- PWMWNFMRSKOCEY-UHFFFAOYSA-N 1-Phenyl-1,2-ethanediol Chemical compound OCC(O)C1=CC=CC=C1 PWMWNFMRSKOCEY-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 description 3
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 description 3
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 description 3
- 241000416162 Astragalus gummifer Species 0.000 description 3
- 206010008089 Cerebral artery occlusion Diseases 0.000 description 3
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 3
- 208000026331 Disruptive, Impulse Control, and Conduct disease Diseases 0.000 description 3
- 102000004190 Enzymes Human genes 0.000 description 3
- 108090000790 Enzymes Proteins 0.000 description 3
- 102000018899 Glutamate Receptors Human genes 0.000 description 3
- 108010027915 Glutamate Receptors Proteins 0.000 description 3
- 101000666657 Homo sapiens Rho-related GTP-binding protein RhoQ Proteins 0.000 description 3
- 208000030990 Impulse-control disease Diseases 0.000 description 3
- 206010061218 Inflammation Diseases 0.000 description 3
- 229930195725 Mannitol Natural products 0.000 description 3
- 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 3
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 102100038339 Rho-related GTP-binding protein RhoQ Human genes 0.000 description 3
- 208000003954 Spinal Muscular Atrophies of Childhood Diseases 0.000 description 3
- 229920001615 Tragacanth Polymers 0.000 description 3
- 235000010489 acacia gum Nutrition 0.000 description 3
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 230000002378 acidificating effect Effects 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 description 3
- 238000000540 analysis of variance Methods 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000003963 antioxidant agent Substances 0.000 description 3
- 235000006708 antioxidants Nutrition 0.000 description 3
- 210000001130 astrocyte Anatomy 0.000 description 3
- 230000002146 bilateral effect Effects 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- 230000006931 brain damage Effects 0.000 description 3
- 231100000874 brain damage Toxicity 0.000 description 3
- 208000029028 brain injury Diseases 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 239000002775 capsule Substances 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000006243 chemical reaction Methods 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
- 239000003086 colorant Substances 0.000 description 3
- 230000000875 corresponding effect Effects 0.000 description 3
- 230000003111 delayed effect Effects 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 238000009826 distribution Methods 0.000 description 3
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 3
- 230000002124 endocrine Effects 0.000 description 3
- 239000000835 fiber Substances 0.000 description 3
- 235000013355 food flavoring agent Nutrition 0.000 description 3
- 235000003599 food sweetener Nutrition 0.000 description 3
- 230000002068 genetic effect Effects 0.000 description 3
- 230000007574 infarction Effects 0.000 description 3
- 230000002401 inhibitory effect Effects 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 230000002045 lasting effect Effects 0.000 description 3
- 239000000594 mannitol Substances 0.000 description 3
- 235000010355 mannitol Nutrition 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 239000003550 marker Substances 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000002503 metabolic effect Effects 0.000 description 3
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 3
- 229960001383 methylscopolamine Drugs 0.000 description 3
- 201000007309 middle cerebral artery infarction Diseases 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 208000005264 motor neuron disease Diseases 0.000 description 3
- 210000001577 neostriatum Anatomy 0.000 description 3
- 208000028412 nervous system injury Diseases 0.000 description 3
- 238000001543 one-way ANOVA Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 102000004169 proteins and genes Human genes 0.000 description 3
- 238000001650 pulsed electrochemical detection Methods 0.000 description 3
- 238000011552 rat model Methods 0.000 description 3
- 230000000384 rearing effect Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000010410 reperfusion Effects 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 208000022610 schizoaffective disease Diseases 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 208000002320 spinal muscular atrophy Diseases 0.000 description 3
- 230000000638 stimulation Effects 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 210000003523 substantia nigra Anatomy 0.000 description 3
- 239000000829 suppository Substances 0.000 description 3
- 239000000375 suspending agent Substances 0.000 description 3
- 239000003765 sweetening agent Substances 0.000 description 3
- 210000000225 synapse Anatomy 0.000 description 3
- 239000006188 syrup Substances 0.000 description 3
- 235000020357 syrup Nutrition 0.000 description 3
- 230000003442 weekly effect Effects 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- 244000215068 Acacia senegal Species 0.000 description 2
- 235000006491 Acacia senegal Nutrition 0.000 description 2
- 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 2
- 208000037259 Amyloid Plaque Diseases 0.000 description 2
- 235000003911 Arachis Nutrition 0.000 description 2
- 244000105624 Arachis hypogaea Species 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000020925 Bipolar disease Diseases 0.000 description 2
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 2
- 201000006474 Brain Ischemia Diseases 0.000 description 2
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 206010008120 Cerebral ischaemia Diseases 0.000 description 2
- 206010012735 Diarrhoea Diseases 0.000 description 2
- 208000001730 Familial dysautonomia Diseases 0.000 description 2
- 201000011240 Frontotemporal dementia Diseases 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 229920000084 Gum arabic Polymers 0.000 description 2
- 206010019196 Head injury Diseases 0.000 description 2
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 description 2
- 206010021002 Hypoglycaemic encephalopathy Diseases 0.000 description 2
- 206010061216 Infarction Diseases 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- 208000034693 Laceration Diseases 0.000 description 2
- 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 2
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
- 108010025020 Nerve Growth Factor Proteins 0.000 description 2
- 208000012902 Nervous system disease Diseases 0.000 description 2
- 206010029350 Neurotoxicity Diseases 0.000 description 2
- 208000000609 Pick Disease of the Brain Diseases 0.000 description 2
- 206010035039 Piloerection Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 208000033526 Proximal spinal muscular atrophy type 3 Diseases 0.000 description 2
- 241000700157 Rattus norvegicus Species 0.000 description 2
- 201000001638 Riley-Day syndrome Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 238000000692 Student's t-test Methods 0.000 description 2
- 206010044221 Toxic encephalopathy Diseases 0.000 description 2
- 229910052770 Uranium Inorganic materials 0.000 description 2
- 201000004810 Vascular dementia Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 238000002835 absorbance Methods 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 2
- 230000004075 alteration Effects 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000006907 apoptotic process Effects 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- 239000002585 base Substances 0.000 description 2
- 239000006172 buffering agent Substances 0.000 description 2
- 229910052791 calcium Inorganic materials 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 210000005056 cell body Anatomy 0.000 description 2
- 230000001413 cellular effect Effects 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- 230000001055 chewing effect Effects 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 230000006726 chronic neurodegeneration Effects 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 239000003179 convulsant agent Substances 0.000 description 2
- 230000000254 damaging effect Effects 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002270 dispersing agent Substances 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000008298 dragée Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 230000021824 exploration behavior Effects 0.000 description 2
- 239000012091 fetal bovine serum Substances 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 210000003194 forelimb Anatomy 0.000 description 2
- 235000011187 glycerol Nutrition 0.000 description 2
- 238000011194 good manufacturing practice Methods 0.000 description 2
- 210000004565 granule cell Anatomy 0.000 description 2
- 244000144993 groups of animals Species 0.000 description 2
- BXWNKGSJHAJOGX-UHFFFAOYSA-N hexadecan-1-ol Chemical compound CCCCCCCCCCCCCCCCO BXWNKGSJHAJOGX-UHFFFAOYSA-N 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000006698 induction Effects 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000000977 initiatory effect Effects 0.000 description 2
- 238000007917 intracranial administration Methods 0.000 description 2
- 201000004815 juvenile spinal muscular atrophy Diseases 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- 201000010901 lateral sclerosis Diseases 0.000 description 2
- 210000004199 lateral thalamic nuclei Anatomy 0.000 description 2
- 231100000225 lethality Toxicity 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 239000007937 lozenge 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
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 239000002480 mineral oil Substances 0.000 description 2
- 235000010446 mineral oil Nutrition 0.000 description 2
- 239000002052 molecular layer Substances 0.000 description 2
- 229910052750 molybdenum Inorganic materials 0.000 description 2
- 210000000478 neocortex Anatomy 0.000 description 2
- 230000000626 neurodegenerative effect Effects 0.000 description 2
- 210000004498 neuroglial cell Anatomy 0.000 description 2
- 230000000926 neurological effect Effects 0.000 description 2
- 230000007135 neurotoxicity Effects 0.000 description 2
- 231100000228 neurotoxicity Toxicity 0.000 description 2
- 239000000346 nonvolatile oil Substances 0.000 description 2
- 239000012053 oil suspension Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 230000000149 penetrating effect Effects 0.000 description 2
- 229960001412 pentobarbital Drugs 0.000 description 2
- 230000009984 peri-natal effect Effects 0.000 description 2
- 208000033808 peripheral neuropathy Diseases 0.000 description 2
- 208000022821 personality disease Diseases 0.000 description 2
- 238000011458 pharmacological treatment Methods 0.000 description 2
- 208000028591 pheochromocytoma Diseases 0.000 description 2
- 239000008363 phosphate buffer Substances 0.000 description 2
- 239000006187 pill Substances 0.000 description 2
- 229960002139 pilocarpine hydrochloride Drugs 0.000 description 2
- RNAICSBVACLLGM-GNAZCLTHSA-N pilocarpine hydrochloride Chemical compound Cl.C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C RNAICSBVACLLGM-GNAZCLTHSA-N 0.000 description 2
- 230000005371 pilomotor reflex Effects 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 2
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 238000002600 positron emission tomography Methods 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 201000002212 progressive supranuclear palsy Diseases 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 2
- 210000001525 retina Anatomy 0.000 description 2
- 230000033764 rhythmic process Effects 0.000 description 2
- 238000006748 scratching Methods 0.000 description 2
- 230000002393 scratching effect Effects 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 239000012679 serum free medium Substances 0.000 description 2
- SQGYOTSLMSWVJD-UHFFFAOYSA-N silver(1+) nitrate Chemical compound [Ag+].[O-]N(=O)=O SQGYOTSLMSWVJD-UHFFFAOYSA-N 0.000 description 2
- 210000003625 skull Anatomy 0.000 description 2
- 235000015424 sodium Nutrition 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012439 solid excipient Substances 0.000 description 2
- 208000020431 spinal cord injury Diseases 0.000 description 2
- 238000012453 sprague-dawley rat model Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 230000008093 supporting effect Effects 0.000 description 2
- 230000000946 synaptic effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 238000007910 systemic administration Methods 0.000 description 2
- 230000000542 thalamic effect Effects 0.000 description 2
- 210000004001 thalamic nuclei Anatomy 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 239000002562 thickening agent Substances 0.000 description 2
- KUUVQVSHGLHAKZ-UHFFFAOYSA-N thionine Chemical compound C=1C=CC=CSC=CC=1 KUUVQVSHGLHAKZ-UHFFFAOYSA-N 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 201000010875 transient cerebral ischemia Diseases 0.000 description 2
- 208000032527 type III spinal muscular atrophy Diseases 0.000 description 2
- 235000015112 vegetable and seed oil Nutrition 0.000 description 2
- 239000008158 vegetable oil Substances 0.000 description 2
- 210000005111 ventral hippocampus Anatomy 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- WRIDQFICGBMAFQ-UHFFFAOYSA-N (E)-8-Octadecenoic acid Natural products CCCCCCCCCC=CCCCCCCC(O)=O WRIDQFICGBMAFQ-UHFFFAOYSA-N 0.000 description 1
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- ZORQXIQZAOLNGE-UHFFFAOYSA-N 1,1-difluorocyclohexane Chemical compound FC1(F)CCCCC1 ZORQXIQZAOLNGE-UHFFFAOYSA-N 0.000 description 1
- JLPULHDHAOZNQI-ZTIMHPMXSA-N 1-hexadecanoyl-2-(9Z,12Z-octadecadienoyl)-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCCCCCC\C=C/C\C=C/CCCCC JLPULHDHAOZNQI-ZTIMHPMXSA-N 0.000 description 1
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 1
- LQJBNNIYVWPHFW-UHFFFAOYSA-N 20:1omega9c fatty acid Natural products CCCCCCCCCCC=CCCCCCCCC(O)=O LQJBNNIYVWPHFW-UHFFFAOYSA-N 0.000 description 1
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 1
- CYDQOEWLBCCFJZ-UHFFFAOYSA-N 4-(4-fluorophenyl)oxane-4-carboxylic acid Chemical compound C=1C=C(F)C=CC=1C1(C(=O)O)CCOCC1 CYDQOEWLBCCFJZ-UHFFFAOYSA-N 0.000 description 1
- QSBYPNXLFMSGKH-UHFFFAOYSA-N 9-Heptadecensaeure Natural products CCCCCCCC=CCCCCCCCC(O)=O QSBYPNXLFMSGKH-UHFFFAOYSA-N 0.000 description 1
- 208000030090 Acute Disease Diseases 0.000 description 1
- 201000011452 Adrenoleukodystrophy Diseases 0.000 description 1
- 208000018126 Adrenomyeloneuropathy Diseases 0.000 description 1
- 229920001817 Agar Polymers 0.000 description 1
- 206010001497 Agitation Diseases 0.000 description 1
- 206010001541 Akinesia Diseases 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 102000013455 Amyloid beta-Peptides Human genes 0.000 description 1
- 108010090849 Amyloid beta-Peptides Proteins 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 108010011485 Aspartame Proteins 0.000 description 1
- 206010003591 Ataxia Diseases 0.000 description 1
- 206010003594 Ataxia telangiectasia Diseases 0.000 description 1
- 102000007371 Ataxin-3 Human genes 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 208000021657 Birth injury Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- 206010006542 Bulbar palsy Diseases 0.000 description 1
- 206010068597 Bulbospinal muscular atrophy congenital Diseases 0.000 description 1
- YDNKGFDKKRUKPY-JHOUSYSJSA-N C16 ceramide Natural products CCCCCCCCCCCCCCCC(=O)N[C@@H](CO)[C@H](O)C=CCCCCCCCCCCCCC YDNKGFDKKRUKPY-JHOUSYSJSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- 108010076667 Caspases Proteins 0.000 description 1
- 102000011727 Caspases Human genes 0.000 description 1
- 208000014912 Central Nervous System Infections Diseases 0.000 description 1
- 206010058842 Cerebrovascular insufficiency Diseases 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- 208000010693 Charcot-Marie-Tooth Disease Diseases 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 206010057645 Chronic Inflammatory Demyelinating Polyradiculoneuropathy Diseases 0.000 description 1
- 208000030939 Chronic inflammatory demyelinating polyneuropathy Diseases 0.000 description 1
- 208000033647 Classic progressive supranuclear palsy syndrome Diseases 0.000 description 1
- 206010053398 Clonic convulsion Diseases 0.000 description 1
- 102000008186 Collagen Human genes 0.000 description 1
- 108010035532 Collagen Proteins 0.000 description 1
- 241001573498 Compacta Species 0.000 description 1
- 208000034656 Contusions Diseases 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 201000000077 Cysticercosis Diseases 0.000 description 1
- 101710088194 Dehydrogenase Proteins 0.000 description 1
- 206010067889 Dementia with Lewy bodies Diseases 0.000 description 1
- 239000004338 Dichlorodifluoromethane Substances 0.000 description 1
- 208000001654 Drug Resistant Epilepsy Diseases 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 206010073681 Epidural haemorrhage Diseases 0.000 description 1
- 241000282324 Felis Species 0.000 description 1
- 229940123457 Free radical scavenger Drugs 0.000 description 1
- 208000024412 Friedreich ataxia Diseases 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Chemical compound OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 229940086575 Glutamate release inhibitor Drugs 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 208000035895 Guillain-Barré syndrome Diseases 0.000 description 1
- 206010018985 Haemorrhage intracranial Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- 206010020751 Hypersensitivity Diseases 0.000 description 1
- 208000008574 Intracranial Hemorrhages Diseases 0.000 description 1
- 208000027747 Kennedy disease Diseases 0.000 description 1
- CKLJMWTZIZZHCS-REOHCLBHSA-N L-aspartic acid Chemical compound OC(=O)[C@@H](N)CC(O)=O CKLJMWTZIZZHCS-REOHCLBHSA-N 0.000 description 1
- 201000010743 Lambert-Eaton myasthenic syndrome Diseases 0.000 description 1
- 208000001393 Lathyrism Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 208000034800 Leukoencephalopathies Diseases 0.000 description 1
- 208000009829 Lewy Body Disease Diseases 0.000 description 1
- 238000000719 MTS assay Methods 0.000 description 1
- 231100000070 MTS assay Toxicity 0.000 description 1
- 208000002569 Machado-Joseph Disease Diseases 0.000 description 1
- 208000019090 Machado-Joseph disease type 3 Diseases 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000026139 Memory disease Diseases 0.000 description 1
- 208000026680 Metabolic Brain disease Diseases 0.000 description 1
- 206010062190 Metabolic encephalopathy Diseases 0.000 description 1
- 201000011442 Metachromatic leukodystrophy Diseases 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 206010049567 Miller Fisher syndrome Diseases 0.000 description 1
- 208000019022 Mood disease Diseases 0.000 description 1
- 241001529936 Murinae Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000002740 Muscle Rigidity Diseases 0.000 description 1
- 208000002033 Myoclonus Diseases 0.000 description 1
- CRJGESKKUOMBCT-VQTJNVASSA-N N-acetylsphinganine Chemical compound CCCCCCCCCCCCCCC[C@@H](O)[C@H](CO)NC(C)=O CRJGESKKUOMBCT-VQTJNVASSA-N 0.000 description 1
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 206010050081 Neonatal hypoxia Diseases 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 206010060860 Neurological symptom Diseases 0.000 description 1
- 239000005642 Oleic acid Substances 0.000 description 1
- ZQPPMHVWECSIRJ-UHFFFAOYSA-N Oleic acid Natural products CCCCCCCCC=CCCCCCCCC(O)=O ZQPPMHVWECSIRJ-UHFFFAOYSA-N 0.000 description 1
- 241000283973 Oryctolagus cuniculus Species 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 206010033799 Paralysis Diseases 0.000 description 1
- 206010033885 Paraparesis Diseases 0.000 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 208000005374 Poisoning Diseases 0.000 description 1
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 1
- 229920002565 Polyethylene Glycol 400 Polymers 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 241000097929 Porphyria Species 0.000 description 1
- 208000010642 Porphyrias Diseases 0.000 description 1
- 206010036590 Premature baby Diseases 0.000 description 1
- 208000032319 Primary lateral sclerosis Diseases 0.000 description 1
- 102000029797 Prion Human genes 0.000 description 1
- 108091000054 Prion Proteins 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 208000032225 Proximal spinal muscular atrophy type 1 Diseases 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- 239000012980 RPMI-1640 medium Substances 0.000 description 1
- 208000019155 Radiation injury Diseases 0.000 description 1
- 208000005587 Refsum Disease Diseases 0.000 description 1
- 208000021811 Sandhoff disease Diseases 0.000 description 1
- 208000034189 Sclerosis Diseases 0.000 description 1
- 208000009106 Shy-Drager Syndrome Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 208000002548 Spastic Paraparesis Diseases 0.000 description 1
- 208000036834 Spinocerebellar ataxia type 3 Diseases 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 208000037065 Subacute sclerosing leukoencephalitis Diseases 0.000 description 1
- 206010042297 Subacute sclerosing panencephalitis Diseases 0.000 description 1
- 208000032851 Subarachnoid Hemorrhage Diseases 0.000 description 1
- 206010042364 Subdural haemorrhage Diseases 0.000 description 1
- 208000032859 Synucleinopathies Diseases 0.000 description 1
- 208000022292 Tay-Sachs disease Diseases 0.000 description 1
- 208000007536 Thrombosis Diseases 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- GSEJCLTVZPLZKY-UHFFFAOYSA-N Triethanolamine Chemical compound OCCN(CCO)CCO GSEJCLTVZPLZKY-UHFFFAOYSA-N 0.000 description 1
- 235000021307 Triticum Nutrition 0.000 description 1
- 244000098338 Triticum aestivum Species 0.000 description 1
- 206010046298 Upper motor neurone lesion Diseases 0.000 description 1
- 206010063661 Vascular encephalopathy Diseases 0.000 description 1
- 208000026481 Werdnig-Hoffmann disease Diseases 0.000 description 1
- 208000006269 X-Linked Bulbo-Spinal Atrophy Diseases 0.000 description 1
- 241000209149 Zea Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- APERIXFHHNDFQV-UHFFFAOYSA-N [2-[2-[2-[bis(carboxymethyl)amino]-5-methylphenoxy]ethoxy]-4-[3,6-bis(dimethylamino)xanthen-9-ylidene]cyclohexa-2,5-dien-1-ylidene]-bis(carboxymethyl)azanium;chloride Chemical compound [Cl-].C12=CC=C(N(C)C)C=C2OC2=CC(N(C)C)=CC=C2C1=C(C=1)C=CC(=[N+](CC(O)=O)CC(O)=O)C=1OCCOC1=CC(C)=CC=C1N(CC(O)=O)CC(O)=O APERIXFHHNDFQV-UHFFFAOYSA-N 0.000 description 1
- ZHAFUINZIZIXFC-UHFFFAOYSA-N [9-(dimethylamino)-10-methylbenzo[a]phenoxazin-5-ylidene]azanium;chloride Chemical compound [Cl-].O1C2=CC(=[NH2+])C3=CC=CC=C3C2=NC2=C1C=C(N(C)C)C(C)=C2 ZHAFUINZIZIXFC-UHFFFAOYSA-N 0.000 description 1
- 230000005856 abnormality Effects 0.000 description 1
- 239000001785 acacia senegal l. willd gum Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 208000030597 adult Refsum disease Diseases 0.000 description 1
- 239000008272 agar Substances 0.000 description 1
- 235000010419 agar Nutrition 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 208000029650 alcohol withdrawal Diseases 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
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000002947 alkylene group Chemical group 0.000 description 1
- 208000026935 allergic disease Diseases 0.000 description 1
- 230000007815 allergy Effects 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 210000002551 anterior cerebral artery Anatomy 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 230000009925 apoptotic mechanism Effects 0.000 description 1
- 101150031224 app gene Proteins 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
- 239000000605 aspartame Substances 0.000 description 1
- 235000010357 aspartame Nutrition 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
- 229960003438 aspartame Drugs 0.000 description 1
- 229940009098 aspartate Drugs 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 230000003416 augmentation Effects 0.000 description 1
- 230000002567 autonomic effect Effects 0.000 description 1
- 210000003050 axon Anatomy 0.000 description 1
- 230000001580 bacterial effect Effects 0.000 description 1
- 235000013871 bee wax Nutrition 0.000 description 1
- 239000012166 beeswax Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 125000001743 benzylic group Chemical group 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 230000036765 blood level Effects 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000005978 brain dysfunction Effects 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 235000011148 calcium chloride Nutrition 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 108010079785 calpain inhibitors Proteins 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001722 carbon compounds Chemical class 0.000 description 1
- 210000004004 carotid artery internal Anatomy 0.000 description 1
- 230000005779 cell damage Effects 0.000 description 1
- 208000037887 cell injury Diseases 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 229940106189 ceramide Drugs 0.000 description 1
- ZVEQCJWYRWKARO-UHFFFAOYSA-N ceramide Natural products CCCCCCCCCCCCCCC(O)C(=O)NC(CO)C(O)C=CCCC=C(C)CCCCCCCCC ZVEQCJWYRWKARO-UHFFFAOYSA-N 0.000 description 1
- 206010008129 cerebral palsy Diseases 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 229960000541 cetyl alcohol Drugs 0.000 description 1
- 230000009920 chelation Effects 0.000 description 1
- 238000000546 chi-square test Methods 0.000 description 1
- 210000000349 chromosome Anatomy 0.000 description 1
- 229940110456 cocoa butter Drugs 0.000 description 1
- 235000019868 cocoa butter Nutrition 0.000 description 1
- 239000003240 coconut oil Substances 0.000 description 1
- 235000019864 coconut oil Nutrition 0.000 description 1
- 229920001436 collagen Polymers 0.000 description 1
- 229940075614 colloidal silicon dioxide Drugs 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 230000001010 compromised effect Effects 0.000 description 1
- 230000009519 contusion Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000009509 cortical damage Effects 0.000 description 1
- 210000003792 cranial nerve Anatomy 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 210000004748 cultured cell Anatomy 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 208000017004 dementia pugilistica Diseases 0.000 description 1
- 230000003210 demyelinating effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000013400 design of experiment Methods 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 230000001627 detrimental effect Effects 0.000 description 1
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 description 1
- 235000019404 dichlorodifluoromethane Nutrition 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 239000000539 dimer Substances 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- VDQVEACBQKUUSU-UHFFFAOYSA-M disodium;sulfanide Chemical compound [Na+].[Na+].[SH-] VDQVEACBQKUUSU-UHFFFAOYSA-M 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 210000005064 dopaminergic neuron Anatomy 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 210000005110 dorsal hippocampus Anatomy 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000002900 effect on cell Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 230000003073 embolic effect Effects 0.000 description 1
- 239000003974 emollient agent Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000012202 endocytosis Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 231100000318 excitotoxic Toxicity 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000003414 extremity Anatomy 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000001097 facial muscle Anatomy 0.000 description 1
- 201000006061 fatal familial insomnia Diseases 0.000 description 1
- 230000008175 fetal development Effects 0.000 description 1
- 235000019634 flavors Nutrition 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 239000012737 fresh medium Substances 0.000 description 1
- 210000001652 frontal lobe Anatomy 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 230000003371 gabaergic effect Effects 0.000 description 1
- 150000002270 gangliosides Chemical class 0.000 description 1
- 238000011223 gene expression profiling Methods 0.000 description 1
- 230000002518 glial effect Effects 0.000 description 1
- 230000004153 glucose metabolism Effects 0.000 description 1
- 239000003825 glutamate receptor antagonist Substances 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 230000002641 glycemic effect Effects 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 238000000227 grinding Methods 0.000 description 1
- 239000001963 growth medium Substances 0.000 description 1
- 229940093915 gynecological organic acid Drugs 0.000 description 1
- 230000002440 hepatic effect Effects 0.000 description 1
- 208000008675 hereditary spastic paraplegia Diseases 0.000 description 1
- FBPFZTCFMRRESA-UHFFFAOYSA-N hexane-1,2,3,4,5,6-hexol Chemical compound OCC(O)C(O)C(O)C(O)CO FBPFZTCFMRRESA-UHFFFAOYSA-N 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 210000001879 hippocampal ca1 region Anatomy 0.000 description 1
- 210000001661 hippocampal ca3 region Anatomy 0.000 description 1
- HNDVDQJCIGZPNO-UHFFFAOYSA-N histidine Natural products OC(=O)C(N)CC1=CN=CN1 HNDVDQJCIGZPNO-UHFFFAOYSA-N 0.000 description 1
- 230000003118 histopathologic effect Effects 0.000 description 1
- 150000002430 hydrocarbons Chemical group 0.000 description 1
- 229920003063 hydroxymethyl cellulose Polymers 0.000 description 1
- 229940031574 hydroxymethyl cellulose Drugs 0.000 description 1
- 208000013403 hyperactivity Diseases 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 208000026278 immune system disease Diseases 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000002513 implantation Methods 0.000 description 1
- 230000001976 improved effect Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010874 in vitro model Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 230000006882 induction of apoptosis Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002458 infectious effect Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000008798 inflammatory stress Effects 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 229940102223 injectable solution Drugs 0.000 description 1
- 229940102213 injectable suspension Drugs 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000002109 interictal effect Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 208000020658 intracerebral hemorrhage Diseases 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 208000037906 ischaemic injury Diseases 0.000 description 1
- QXJSBBXBKPUZAA-UHFFFAOYSA-N isooleic acid Natural products CCCCCCCC=CCCCCCCCCC(O)=O QXJSBBXBKPUZAA-UHFFFAOYSA-N 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 229960003299 ketamine Drugs 0.000 description 1
- 206010023497 kuru Diseases 0.000 description 1
- 238000002372 labelling Methods 0.000 description 1
- 230000013016 learning Effects 0.000 description 1
- 201000003723 learning disability Diseases 0.000 description 1
- 235000010445 lecithin Nutrition 0.000 description 1
- 239000000787 lecithin Substances 0.000 description 1
- 229940067606 lecithin Drugs 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 230000005923 long-lasting effect Effects 0.000 description 1
- 239000008176 lyophilized powder Substances 0.000 description 1
- 239000011777 magnesium Substances 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
- 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
- 238000005259 measurement Methods 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000015654 memory Effects 0.000 description 1
- 230000006984 memory degeneration Effects 0.000 description 1
- 208000023060 memory loss Diseases 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 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
- 210000003657 middle cerebral artery Anatomy 0.000 description 1
- 229960003248 mifepristone Drugs 0.000 description 1
- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000002438 mitochondrial effect Effects 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000000051 modifying effect Effects 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 201000000585 muscular atrophy Diseases 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- VMGAPWLDMVPYIA-HIDZBRGKSA-N n'-amino-n-iminomethanimidamide Chemical compound N\N=C\N=N VMGAPWLDMVPYIA-HIDZBRGKSA-N 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 208000020469 nerve plexus disease Diseases 0.000 description 1
- 230000007472 neurodevelopment Effects 0.000 description 1
- 210000002682 neurofibrillary tangle Anatomy 0.000 description 1
- 238000002610 neuroimaging Methods 0.000 description 1
- 238000010984 neurological examination Methods 0.000 description 1
- 230000007991 neuronal integrity Effects 0.000 description 1
- 230000007512 neuronal protection Effects 0.000 description 1
- 230000003982 neuronal uptake Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 230000007171 neuropathology Effects 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- VVGIYYKRAMHVLU-UHFFFAOYSA-N newbouldiamide Natural products CCCCCCCCCCCCCCCCCCCC(O)C(O)C(O)C(CO)NC(=O)CCCCCCCCCCCCCCCCC VVGIYYKRAMHVLU-UHFFFAOYSA-N 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 231100000344 non-irritating Toxicity 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- GYCKQBWUSACYIF-UHFFFAOYSA-N o-hydroxybenzoic acid ethyl ester Natural products CCOC(=O)C1=CC=CC=C1O GYCKQBWUSACYIF-UHFFFAOYSA-N 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
- 239000002674 ointment Substances 0.000 description 1
- ZQPPMHVWECSIRJ-KTKRTIGZSA-N oleic acid Chemical compound CCCCCCCC\C=C/CCCCCCCC(O)=O ZQPPMHVWECSIRJ-KTKRTIGZSA-N 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 229940005483 opioid analgesics Drugs 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 230000036542 oxidative stress Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000003002 pH adjusting agent Substances 0.000 description 1
- 239000003973 paint Substances 0.000 description 1
- 239000012188 paraffin wax Substances 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000001936 parietal effect Effects 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010603 pastilles Nutrition 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 238000003359 percent control normalization Methods 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000004962 physiological condition Effects 0.000 description 1
- 230000003169 placental effect Effects 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 201000006380 plexopathy Diseases 0.000 description 1
- 231100000572 poisoning Toxicity 0.000 description 1
- 230000000607 poisoning effect Effects 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000013641 positive control Substances 0.000 description 1
- 210000003388 posterior cerebral artery Anatomy 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 208000001282 primary progressive aphasia Diseases 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 208000032207 progressive 1 supranuclear palsy Diseases 0.000 description 1
- 201000002241 progressive bulbar palsy Diseases 0.000 description 1
- 206010036807 progressive multifocal leukoencephalopathy Diseases 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000006337 proteolytic cleavage Effects 0.000 description 1
- 201000000196 pseudobulbar palsy Diseases 0.000 description 1
- 229940001470 psychoactive drug Drugs 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 239000002516 radical scavenger Substances 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 210000000664 rectum Anatomy 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 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 1
- 230000004044 response Effects 0.000 description 1
- 230000011506 response to oxidative stress Effects 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 235000019204 saccharin Nutrition 0.000 description 1
- CVHZOJJKTDOEJC-UHFFFAOYSA-N saccharin Chemical compound C1=CC=C2C(=O)NS(=O)(=O)C2=C1 CVHZOJJKTDOEJC-UHFFFAOYSA-N 0.000 description 1
- 229940081974 saccharin Drugs 0.000 description 1
- 239000000901 saccharin and its Na,K and Ca salt Substances 0.000 description 1
- 230000011218 segmentation Effects 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- 238000009097 single-agent therapy Methods 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 239000001540 sodium lactate Substances 0.000 description 1
- 229940005581 sodium lactate Drugs 0.000 description 1
- 235000011088 sodium lactate Nutrition 0.000 description 1
- 229910052979 sodium sulfide Inorganic materials 0.000 description 1
- 235000011069 sorbitan monooleate Nutrition 0.000 description 1
- 239000001593 sorbitan monooleate Substances 0.000 description 1
- 229940035049 sorbitan monooleate Drugs 0.000 description 1
- 229940083466 soybean lecithin Drugs 0.000 description 1
- 230000001148 spastic effect Effects 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 238000012421 spiking Methods 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000011272 standard treatment Methods 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 208000003755 striatonigral degeneration Diseases 0.000 description 1
- 238000010254 subcutaneous injection Methods 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 230000005062 synaptic transmission Effects 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 238000012353 t test Methods 0.000 description 1
- 208000004441 taeniasis Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 239000003104 tissue culture media Substances 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000010487 tragacanth Nutrition 0.000 description 1
- 239000000196 tragacanth Substances 0.000 description 1
- 229940116362 tragacanth Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical class [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 208000032471 type 1 spinal muscular atrophy Diseases 0.000 description 1
- 229940072690 valium Drugs 0.000 description 1
- 210000002071 ventral thalamic nuclei Anatomy 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
- 210000004127 vitreous body Anatomy 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/325—Carbamic acids; Thiocarbamic acids; Anhydrides or salts thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61P21/04—Drugs for disorders of the muscular or neuromuscular system for myasthenia gravis
-
- 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
- A61P25/08—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
- A61P25/28—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
- A61P25/32—Alcohol-abuse
-
- 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
- A61P25/36—Opioid-abuse
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Addiction (AREA)
- Diabetes (AREA)
- Psychology (AREA)
- Emergency Medicine (AREA)
- Hospice & Palliative Care (AREA)
- Cardiology (AREA)
- Vascular Medicine (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Hematology (AREA)
- Heart & Thoracic Surgery (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (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 |
|---|---|---|---|
| US69840305P | 2005-07-12 | 2005-07-12 | |
| US60/698,403 | 2005-07-12 | ||
| PCT/US2006/026291 WO2007008562A2 (en) | 2005-07-12 | 2006-07-07 | Carbamate compounds for use in treating neurodegenerative disorders |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2615129A1 true CA2615129A1 (en) | 2007-01-18 |
Family
ID=37637734
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002615129A Abandoned CA2615129A1 (en) | 2005-07-12 | 2006-07-07 | Carbamate compounds for use in treating neurodegenerative disorders |
Country Status (18)
| Country | Link |
|---|---|
| US (2) | US20070021500A1 (https=) |
| EP (1) | EP1917009A2 (https=) |
| JP (1) | JP2009501224A (https=) |
| KR (1) | KR20080031951A (https=) |
| CN (1) | CN101287459A (https=) |
| AR (1) | AR054551A1 (https=) |
| AU (1) | AU2006269381A1 (https=) |
| BR (1) | BRPI0613006A2 (https=) |
| CA (1) | CA2615129A1 (https=) |
| CR (1) | CR9721A (https=) |
| EA (1) | EA200800294A1 (https=) |
| EC (1) | ECSP088179A (https=) |
| IL (1) | IL188729A0 (https=) |
| NI (1) | NI200800008A (https=) |
| NO (1) | NO20080738L (https=) |
| TW (1) | TW200800158A (https=) |
| WO (1) | WO2007008562A2 (https=) |
| ZA (1) | ZA200801401B (https=) |
Families Citing this family (18)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ES2385087T3 (es) * | 2005-07-26 | 2012-07-18 | Sk Biopharmaceuticals Co., Ltd | Procedimientos para tratar trastornos relacionados con sustancias |
| US9050005B2 (en) | 2005-08-25 | 2015-06-09 | Synapse Biomedical, Inc. | Method and apparatus for transgastric neurostimulation |
| WO2007103585A2 (en) * | 2006-03-09 | 2007-09-13 | Synapse Biomedical, Inc. | Ventilator assist system and method to improve respiratory function |
| US20080097153A1 (en) * | 2006-08-24 | 2008-04-24 | Ignagni Anthony R | Method and apparatus for grasping an abdominal wall |
| JP2010505856A (ja) * | 2006-10-06 | 2010-02-25 | ジヤンセン・フアーマシユーチカ・ナームローゼ・フエンノートシヤツプ | （ｓ）−（＋）−２−（２−クロロフェニル）−２−ヒドロキシ−エチルカルバメートの新規結晶 |
| US9079016B2 (en) * | 2007-02-05 | 2015-07-14 | Synapse Biomedical, Inc. | Removable intramuscular electrode |
| US9820671B2 (en) * | 2007-05-17 | 2017-11-21 | Synapse Biomedical, Inc. | Devices and methods for assessing motor point electromyogram as a biomarker |
| WO2009059033A1 (en) * | 2007-10-30 | 2009-05-07 | Synapse Biomedical, Inc. | Method of improving sleep disordered breathing |
| US8428726B2 (en) | 2007-10-30 | 2013-04-23 | Synapse Biomedical, Inc. | Device and method of neuromodulation to effect a functionally restorative adaption of the neuromuscular system |
| EP2509596B1 (en) | 2009-12-08 | 2019-08-28 | Case Western Reserve University | Gamma aminoacids for treating ocular disorders |
| US8609849B1 (en) | 2010-11-30 | 2013-12-17 | Fox Chase Chemical Diversity Center, Inc. | Hydroxylated sulfamides exhibiting neuroprotective action and their method of use |
| KR101418061B1 (ko) * | 2012-09-28 | 2014-07-10 | 한국과학기술연구원 | 성상교세포의 글루타메이트 방출 기작 |
| CN105189451A (zh) | 2013-03-12 | 2015-12-23 | 比皮艾思药物研发有限公司 | 氨基甲酸苯酯化合物和包含该化合物的用于预防或治疗神经性毒气引起的疾病的组合物 |
| US8652527B1 (en) | 2013-03-13 | 2014-02-18 | Upsher-Smith Laboratories, Inc | Extended-release topiramate capsules |
| US9101545B2 (en) | 2013-03-15 | 2015-08-11 | Upsher-Smith Laboratories, Inc. | Extended-release topiramate capsules |
| WO2017150903A1 (en) | 2016-02-29 | 2017-09-08 | Bio-Pharm Solutions Co., Ltd. | Sulfamate derivative compounds, processes for preparing them and their uses |
| US11471683B2 (en) | 2019-01-29 | 2022-10-18 | Synapse Biomedical, Inc. | Systems and methods for treating sleep apnea using neuromodulation |
| KR20230044274A (ko) * | 2020-08-31 | 2023-04-03 | (주)바이오팜솔루션즈 | 신경퇴행성 질환의 예방 또는 치료용 페닐 알킬 카바메이트 화합물 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5698588A (en) * | 1996-01-16 | 1997-12-16 | Yukong Limited | Halogen substituted carbamate compounds from 2-phenyl-1,2-ethanediol |
| US6306909B1 (en) * | 1997-03-12 | 2001-10-23 | Queen's University At Kingston | Anti-epileptogenic agents |
| HUP0203198A3 (en) * | 1999-08-20 | 2005-07-28 | Ortho Mcneil Pharm Inc | Pharmaceutical composition comprising a tramadol material and an anticonvulsant drug, process for its preparation and its use |
| EP1383489B1 (en) * | 2001-02-27 | 2007-05-09 | Ortho-Mcneil Pharmaceutical, Inc. | Carbamate compounds for use in preventing or treating neurodegenerative disorders |
| DK1809273T3 (da) * | 2004-09-16 | 2010-08-02 | Janssen Pharmaceutica Nv | Anvendelse af 2-phenyl-1,2-ethandiol-(di)carbamater til behandling af epileptogenese |
| PE20070325A1 (es) * | 2005-06-29 | 2007-05-12 | Alza Corp | Formas de dosificacion oral que comprenden compuestos derivados de carbamato |
-
2006
- 2006-07-06 US US11/481,601 patent/US20070021500A1/en not_active Abandoned
- 2006-07-07 WO PCT/US2006/026291 patent/WO2007008562A2/en not_active Ceased
- 2006-07-07 KR KR1020087003268A patent/KR20080031951A/ko not_active Withdrawn
- 2006-07-07 AU AU2006269381A patent/AU2006269381A1/en not_active Abandoned
- 2006-07-07 CN CNA2006800331046A patent/CN101287459A/zh active Pending
- 2006-07-07 EA EA200800294A patent/EA200800294A1/ru unknown
- 2006-07-07 CA CA002615129A patent/CA2615129A1/en not_active Abandoned
- 2006-07-07 BR BRPI0613006-2A patent/BRPI0613006A2/pt not_active IP Right Cessation
- 2006-07-07 JP JP2008521436A patent/JP2009501224A/ja not_active Withdrawn
- 2006-07-07 EP EP06786448A patent/EP1917009A2/en not_active Withdrawn
- 2006-07-11 TW TW095125161A patent/TW200800158A/zh unknown
- 2006-07-11 AR ARP060102977A patent/AR054551A1/es not_active Application Discontinuation
-
2008
- 2008-01-10 IL IL188729A patent/IL188729A0/en unknown
- 2008-01-11 NI NI200800008A patent/NI200800008A/es unknown
- 2008-02-11 ZA ZA200801401A patent/ZA200801401B/xx unknown
- 2008-02-11 NO NO20080738A patent/NO20080738L/no not_active Application Discontinuation
- 2008-02-11 CR CR9721A patent/CR9721A/es unknown
- 2008-02-12 EC EC2008008179A patent/ECSP088179A/es unknown
-
2009
- 2009-01-30 US US12/362,970 patent/US20090137652A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| CR9721A (es) | 2008-11-24 |
| WO2007008562A3 (en) | 2007-08-16 |
| AU2006269381A1 (en) | 2007-01-18 |
| NI200800008A (es) | 2010-11-25 |
| US20070021500A1 (en) | 2007-01-25 |
| AR054551A1 (es) | 2007-06-27 |
| EP1917009A2 (en) | 2008-05-07 |
| EA200800294A1 (ru) | 2008-06-30 |
| KR20080031951A (ko) | 2008-04-11 |
| BRPI0613006A2 (pt) | 2010-12-14 |
| US20090137652A1 (en) | 2009-05-28 |
| ECSP088179A (es) | 2008-03-26 |
| ZA200801401B (en) | 2009-08-26 |
| IL188729A0 (en) | 2008-11-03 |
| TW200800158A (en) | 2008-01-01 |
| JP2009501224A (ja) | 2009-01-15 |
| WO2007008562A2 (en) | 2007-01-18 |
| CN101287459A (zh) | 2008-10-15 |
| NO20080738L (no) | 2008-04-10 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20090137652A1 (en) | Methods for neuroprotection | |
| US20110152362A1 (en) | Methods of treating epileptogenesis and epilepsy | |
| CA2439295C (en) | Carbamate compounds for use in preventing or treating neurodegenerative disorders | |
| US20070021501A1 (en) | Methods of treating epileptogenesis | |
| CA2584854A1 (en) | Carbamate compounds for use in treating neurodegenerative disorders | |
| US20080103198A1 (en) | Methods for treatment of cochlear and vestibular disorders | |
| EP1809273B1 (en) | Use of 2-phenyl-1,2-ethanediol-(di)carbamates for treating epileptogenesis | |
| MX2008000694A (en) | Use of 2-phenyl-l, 2-ethanedi0l-(di) carbamates for treating epileptogenesis and epilepsy | |
| HK1105583B (en) | Use of 2-phenyl-1, 2-ethanediol-(di) carbamates for treating epileptogenesis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |