JP2016204394A - 依存、精神疾患、及び神経変性病の治療のための組成物と方法 - Google Patents
依存、精神疾患、及び神経変性病の治療のための組成物と方法 Download PDFInfo
- Publication number
- JP2016204394A JP2016204394A JP2016177806A JP2016177806A JP2016204394A JP 2016204394 A JP2016204394 A JP 2016204394A JP 2016177806 A JP2016177806 A JP 2016177806A JP 2016177806 A JP2016177806 A JP 2016177806A JP 2016204394 A JP2016204394 A JP 2016204394A
- Authority
- JP
- Japan
- Prior art keywords
- substance
- patient
- pharmaceutical composition
- composition
- compositions
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 183
- 238000000034 method Methods 0.000 title claims abstract description 51
- 230000004770 neurodegeneration Effects 0.000 title claims abstract description 18
- 208000015122 neurodegenerative disease Diseases 0.000 title claims abstract description 18
- 238000011282 treatment Methods 0.000 title claims description 64
- 208000020016 psychiatric disease Diseases 0.000 title description 5
- 239000000126 substance Substances 0.000 claims abstract description 224
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 claims abstract description 176
- 229960000890 hydrocortisone Drugs 0.000 claims abstract description 88
- 230000008499 blood brain barrier function Effects 0.000 claims abstract description 58
- 210000001218 blood-brain barrier Anatomy 0.000 claims abstract description 58
- 230000004179 hypothalamic–pituitary–adrenal axis Effects 0.000 claims abstract description 53
- 239000013543 active substance Substances 0.000 claims abstract description 34
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 33
- 208000019901 Anxiety disease Diseases 0.000 claims abstract description 16
- 230000036506 anxiety Effects 0.000 claims abstract description 16
- FJLBFSROUSIWMA-UHFFFAOYSA-N metyrapone Chemical group C=1C=CN=CC=1C(C)(C)C(=O)C1=CC=CN=C1 FJLBFSROUSIWMA-UHFFFAOYSA-N 0.000 claims description 87
- 229960004465 metyrapone Drugs 0.000 claims description 87
- ADIMAYPTOBDMTL-UHFFFAOYSA-N oxazepam Chemical group C12=CC(Cl)=CC=C2NC(=O)C(O)N=C1C1=CC=CC=C1 ADIMAYPTOBDMTL-UHFFFAOYSA-N 0.000 claims description 85
- 229960004535 oxazepam Drugs 0.000 claims description 84
- 230000000694 effects Effects 0.000 claims description 81
- 239000000055 Corticotropin-Releasing Hormone Substances 0.000 claims description 69
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 69
- 210000002442 prefrontal cortex Anatomy 0.000 claims description 42
- 210000004556 brain Anatomy 0.000 claims description 40
- 108010022152 Corticotropin-Releasing Hormone Proteins 0.000 claims description 36
- 229940041967 corticotropin-releasing hormone Drugs 0.000 claims description 36
- KLVRDXBAMSPYKH-RKYZNNDCSA-N corticotropin-releasing hormone (human) Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)[C@@H](C)CC)NC(=O)[C@H](C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](C)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H]1N(CCC1)C(=O)[C@H]1N(CCC1)C(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](N)CO)[C@@H](C)CC)C(C)C)C(C)C)C1=CNC=N1 KLVRDXBAMSPYKH-RKYZNNDCSA-N 0.000 claims description 36
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 36
- 102400000739 Corticotropin Human genes 0.000 claims description 35
- 101800000414 Corticotropin Proteins 0.000 claims description 35
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=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](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 claims description 35
- 229960000258 corticotropin Drugs 0.000 claims description 35
- 239000008194 pharmaceutical composition Substances 0.000 claims description 35
- 230000014509 gene expression Effects 0.000 claims description 30
- 201000010099 disease Diseases 0.000 claims description 20
- 229940049706 benzodiazepine Drugs 0.000 claims description 13
- XMAYWYJOQHXEEK-ZEQKJWHPSA-N (2S,4R)-ketoconazole Chemical compound C1CN(C(=O)C)CCN1C(C=C1)=CC=C1OC[C@H]1O[C@](CN2C=NC=C2)(C=2C(=CC(Cl)=CC=2)Cl)OC1 XMAYWYJOQHXEEK-ZEQKJWHPSA-N 0.000 claims description 12
- 239000003112 inhibitor Substances 0.000 claims description 11
- 206010012335 Dependence Diseases 0.000 claims description 10
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 10
- 239000002552 dosage form Substances 0.000 claims description 10
- 229960004125 ketoconazole Drugs 0.000 claims description 10
- 230000004060 metabolic process Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 201000000980 schizophrenia Diseases 0.000 claims description 6
- 108010010803 Gelatin Proteins 0.000 claims description 5
- 239000002202 Polyethylene glycol Substances 0.000 claims description 5
- 230000002159 abnormal effect Effects 0.000 claims description 5
- 239000008273 gelatin Substances 0.000 claims description 5
- 229920000159 gelatin Polymers 0.000 claims description 5
- 235000019322 gelatine Nutrition 0.000 claims description 5
- 235000011852 gelatine desserts Nutrition 0.000 claims description 5
- 235000011187 glycerol Nutrition 0.000 claims description 5
- 239000012466 permeate Substances 0.000 claims description 5
- 229920001223 polyethylene glycol Polymers 0.000 claims description 5
- 208000024827 Alzheimer disease Diseases 0.000 claims description 4
- 208000023105 Huntington disease Diseases 0.000 claims description 4
- 208000018737 Parkinson disease Diseases 0.000 claims description 4
- 206010002026 amyotrophic lateral sclerosis Diseases 0.000 claims description 4
- 239000002207 metabolite Substances 0.000 claims description 4
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 claims description 3
- 239000000275 Adrenocorticotropic Hormone Substances 0.000 claims description 3
- 229960004782 chlordiazepoxide Drugs 0.000 claims description 3
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 claims description 3
- 230000003278 mimic effect Effects 0.000 claims description 3
- 238000011200 topical administration Methods 0.000 claims description 3
- 210000004404 adrenal cortex Anatomy 0.000 claims description 2
- 229940064438 nizoral Drugs 0.000 claims description 2
- 230000001817 pituitary effect Effects 0.000 claims description 2
- 102000012289 Corticotropin-Releasing Hormone Human genes 0.000 claims 2
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- 230000002267 hypothalamic effect Effects 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 36
- 210000004100 adrenal gland Anatomy 0.000 abstract description 17
- 239000003795 chemical substances by application Substances 0.000 abstract description 16
- 230000008685 targeting Effects 0.000 abstract description 16
- DDFNHFXLQJLFSX-UHFFFAOYSA-N Metyrapol Chemical compound C=1C=CN=CC=1C(C)(C)C(O)C1=CC=CN=C1 DDFNHFXLQJLFSX-UHFFFAOYSA-N 0.000 abstract description 13
- 238000004519 manufacturing process Methods 0.000 abstract description 9
- 208000028173 post-traumatic stress disease Diseases 0.000 abstract description 7
- 230000021615 conjugation Effects 0.000 abstract description 3
- ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 description 163
- 229960003920 cocaine Drugs 0.000 description 81
- 239000003814 drug Substances 0.000 description 69
- 150000007523 nucleic acids Chemical class 0.000 description 66
- 102000039446 nucleic acids Human genes 0.000 description 64
- 108020004707 nucleic acids Proteins 0.000 description 64
- 241000700159 Rattus Species 0.000 description 58
- 229940079593 drug Drugs 0.000 description 57
- 108090000623 proteins and genes Proteins 0.000 description 46
- 230000004044 response Effects 0.000 description 46
- 235000018102 proteins Nutrition 0.000 description 42
- 102000004169 proteins and genes Human genes 0.000 description 42
- 230000002829 reductive effect Effects 0.000 description 40
- 239000000902 placebo Substances 0.000 description 38
- 229940068196 placebo Drugs 0.000 description 38
- 102100021752 Corticoliberin Human genes 0.000 description 36
- 238000012360 testing method Methods 0.000 description 34
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 33
- 230000035515 penetration Effects 0.000 description 30
- 235000019788 craving Nutrition 0.000 description 29
- 102000005962 receptors Human genes 0.000 description 28
- 108020003175 receptors Proteins 0.000 description 28
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 description 27
- 229960002715 nicotine Drugs 0.000 description 26
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 description 26
- 235000013305 food Nutrition 0.000 description 24
- 210000002820 sympathetic nervous system Anatomy 0.000 description 23
- 238000001802 infusion Methods 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 21
- 230000001419 dependent effect Effects 0.000 description 19
- 239000003981 vehicle Substances 0.000 description 19
- 239000000463 material Substances 0.000 description 18
- 229960001252 methamphetamine Drugs 0.000 description 17
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical compound CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 description 17
- 210000001519 tissue Anatomy 0.000 description 17
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 16
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 16
- 241001465754 Metazoa Species 0.000 description 15
- 230000008901 benefit Effects 0.000 description 15
- 238000009472 formulation Methods 0.000 description 15
- 230000007423 decrease Effects 0.000 description 14
- 239000003446 ligand Substances 0.000 description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
- 230000001965 increasing effect Effects 0.000 description 13
- 239000008186 active pharmaceutical agent Substances 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- GVGYEFKIHJTNQZ-RFQIPJPRSA-N ecgonine benzoate Chemical compound O([C@@H]1[C@@H]([C@H]2CC[C@@H](C1)N2C)C(O)=O)C(=O)C1=CC=CC=C1 GVGYEFKIHJTNQZ-RFQIPJPRSA-N 0.000 description 12
- 238000003786 synthesis reaction Methods 0.000 description 12
- 238000001990 intravenous administration Methods 0.000 description 11
- KZFBHCCLJSAHBQ-UHFFFAOYSA-N Benzoylecgonine Natural products CN1C2CCC1C(C(C2)OC(=C)c3ccccc3)C(=O)O KZFBHCCLJSAHBQ-UHFFFAOYSA-N 0.000 description 10
- 102000008064 Corticotropin Receptors Human genes 0.000 description 10
- 108010074311 Corticotropin Receptors Proteins 0.000 description 10
- 238000002474 experimental method Methods 0.000 description 10
- 230000014759 maintenance of location Effects 0.000 description 10
- JQSHBVHOMNKWFT-DTORHVGOSA-N varenicline Chemical compound C12=CC3=NC=CN=C3C=C2[C@H]2C[C@@H]1CNC2 JQSHBVHOMNKWFT-DTORHVGOSA-N 0.000 description 10
- 229960004751 varenicline Drugs 0.000 description 10
- 108010056643 Corticotropin-Releasing Hormone Receptors Proteins 0.000 description 9
- 150000001557 benzodiazepines Chemical class 0.000 description 9
- 239000012634 fragment Substances 0.000 description 9
- 230000002401 inhibitory effect Effects 0.000 description 9
- 230000009467 reduction Effects 0.000 description 9
- 230000035882 stress Effects 0.000 description 9
- 230000009469 supplementation Effects 0.000 description 9
- 210000002700 urine Anatomy 0.000 description 9
- 230000000692 anti-sense effect Effects 0.000 description 8
- 230000008859 change Effects 0.000 description 8
- 230000007613 environmental effect Effects 0.000 description 8
- 238000002347 injection Methods 0.000 description 8
- 239000007924 injection Substances 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 230000009257 reactivity Effects 0.000 description 8
- 210000002966 serum Anatomy 0.000 description 8
- 238000001356 surgical procedure Methods 0.000 description 8
- 102000005915 GABA Receptors Human genes 0.000 description 7
- 108010005551 GABA Receptors Proteins 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000002411 adverse Effects 0.000 description 7
- 238000000540 analysis of variance Methods 0.000 description 7
- 238000010171 animal model Methods 0.000 description 7
- 239000000074 antisense oligonucleotide Substances 0.000 description 7
- 238000012230 antisense oligonucleotides Methods 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 239000008280 blood Substances 0.000 description 7
- -1 cachets Substances 0.000 description 7
- 125000003729 nucleotide group Chemical group 0.000 description 7
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 238000011084 recovery Methods 0.000 description 7
- 201000009032 substance abuse Diseases 0.000 description 7
- 239000013589 supplement Substances 0.000 description 7
- 239000003826 tablet Substances 0.000 description 7
- 230000001225 therapeutic effect Effects 0.000 description 7
- 239000013598 vector Substances 0.000 description 7
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 6
- 108091030071 RNAI Proteins 0.000 description 6
- 102000007238 Transferrin Receptors Human genes 0.000 description 6
- 108010033576 Transferrin Receptors Proteins 0.000 description 6
- 239000002585 base Substances 0.000 description 6
- 230000006399 behavior Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 239000003184 complementary RNA Substances 0.000 description 6
- 230000003247 decreasing effect Effects 0.000 description 6
- 239000000890 drug combination Substances 0.000 description 6
- 238000007877 drug screening Methods 0.000 description 6
- 230000006870 function Effects 0.000 description 6
- 230000009368 gene silencing by RNA Effects 0.000 description 6
- 239000002773 nucleotide Substances 0.000 description 6
- 230000000638 stimulation Effects 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 229940124597 therapeutic agent Drugs 0.000 description 6
- 238000012549 training Methods 0.000 description 6
- 230000002485 urinary effect Effects 0.000 description 6
- 108020005544 Antisense RNA Proteins 0.000 description 5
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 5
- 210000004731 jugular vein Anatomy 0.000 description 5
- 230000007246 mechanism Effects 0.000 description 5
- 230000000750 progressive effect Effects 0.000 description 5
- AQHHHDLHHXJYJD-UHFFFAOYSA-N propranolol Chemical compound C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 AQHHHDLHHXJYJD-UHFFFAOYSA-N 0.000 description 5
- 230000001105 regulatory effect Effects 0.000 description 5
- 102000004190 Enzymes Human genes 0.000 description 4
- 108090000790 Enzymes Proteins 0.000 description 4
- 241000282412 Homo Species 0.000 description 4
- 108091034117 Oligonucleotide Proteins 0.000 description 4
- VREFGVBLTWBCJP-UHFFFAOYSA-N alprazolam Chemical compound C12=CC(Cl)=CC=C2N2C(C)=NN=C2CN=C1C1=CC=CC=C1 VREFGVBLTWBCJP-UHFFFAOYSA-N 0.000 description 4
- 229960004538 alprazolam Drugs 0.000 description 4
- 238000003556 assay Methods 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 238000004113 cell culture Methods 0.000 description 4
- 206010013663 drug dependence Diseases 0.000 description 4
- 230000036541 health Effects 0.000 description 4
- 230000006872 improvement Effects 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 238000012216 screening Methods 0.000 description 4
- 230000028327 secretion Effects 0.000 description 4
- 208000011117 substance-related disease Diseases 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 108091032973 (ribonucleotides)n+m Proteins 0.000 description 3
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 3
- UGJMXCAKCUNAIE-UHFFFAOYSA-N Gabapentin Chemical compound OC(=O)CC1(CN)CCCCC1 UGJMXCAKCUNAIE-UHFFFAOYSA-N 0.000 description 3
- 108700005091 Immunoglobulin Genes Proteins 0.000 description 3
- 108090000862 Ion Channels Proteins 0.000 description 3
- 102000004310 Ion Channels Human genes 0.000 description 3
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
- 208000027030 Premenstrual dysphoric disease Diseases 0.000 description 3
- 241000700157 Rattus norvegicus Species 0.000 description 3
- 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 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001430 anti-depressive effect Effects 0.000 description 3
- 239000000935 antidepressant agent Substances 0.000 description 3
- 229940005513 antidepressants Drugs 0.000 description 3
- 229940125717 barbiturate Drugs 0.000 description 3
- 230000004888 barrier function Effects 0.000 description 3
- ZRIHAIZYIMGOAB-UHFFFAOYSA-N butabarbital Chemical compound CCC(C)C1(CC)C(=O)NC(=O)NC1=O ZRIHAIZYIMGOAB-UHFFFAOYSA-N 0.000 description 3
- 210000001715 carotid artery Anatomy 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001268 conjugating effect Effects 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 231100000673 dose–response relationship Toxicity 0.000 description 3
- 108010046780 hydrocortisone receptor Proteins 0.000 description 3
- 238000005805 hydroxylation reaction Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 108020004999 messenger RNA Proteins 0.000 description 3
- IUBSYMUCCVWXPE-UHFFFAOYSA-N metoprolol Chemical compound COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 IUBSYMUCCVWXPE-UHFFFAOYSA-N 0.000 description 3
- 210000002569 neuron Anatomy 0.000 description 3
- 239000008188 pellet Substances 0.000 description 3
- 229960001412 pentobarbital Drugs 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 230000011664 signaling Effects 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 231100000736 substance abuse Toxicity 0.000 description 3
- 230000000699 topical effect Effects 0.000 description 3
- 239000012049 topical pharmaceutical composition Substances 0.000 description 3
- 210000005166 vasculature Anatomy 0.000 description 3
- SGUAFYQXFOLMHL-UHFFFAOYSA-N 2-hydroxy-5-{1-hydroxy-2-[(4-phenylbutan-2-yl)amino]ethyl}benzamide Chemical compound C=1C=C(O)C(C(N)=O)=CC=1C(O)CNC(C)CCC1=CC=CC=C1 SGUAFYQXFOLMHL-UHFFFAOYSA-N 0.000 description 2
- 239000003477 4 aminobutyric acid receptor stimulating agent Substances 0.000 description 2
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 description 2
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 2
- USSIQXCVUWKGNF-UHFFFAOYSA-N 6-(dimethylamino)-4,4-diphenylheptan-3-one Chemical compound C=1C=CC=CC=1C(CC(C)N(C)C)(C(=O)CC)C1=CC=CC=C1 USSIQXCVUWKGNF-UHFFFAOYSA-N 0.000 description 2
- KDCGOANMDULRCW-UHFFFAOYSA-N 7H-purine Chemical compound N1=CNC2=NC=NC2=C1 KDCGOANMDULRCW-UHFFFAOYSA-N 0.000 description 2
- 206010001367 Adrenal insufficiency Diseases 0.000 description 2
- 108010078791 Carrier Proteins Proteins 0.000 description 2
- 108010062745 Chloride Channels Proteins 0.000 description 2
- 102000011045 Chloride Channels Human genes 0.000 description 2
- 208000022497 Cocaine-Related disease Diseases 0.000 description 2
- 108091033380 Coding strand Proteins 0.000 description 2
- 241000702421 Dependoparvovirus Species 0.000 description 2
- 238000002965 ELISA Methods 0.000 description 2
- 208000001613 Gambling Diseases 0.000 description 2
- 102000053171 Glial Fibrillary Acidic Human genes 0.000 description 2
- 101710193519 Glial fibrillary acidic protein Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 description 2
- 229930195714 L-glutamate Natural products 0.000 description 2
- ZDXPYRJPNDTMRX-VKHMYHEASA-N L-glutamine Chemical compound OC(=O)[C@@H](N)CCC(N)=O ZDXPYRJPNDTMRX-VKHMYHEASA-N 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
- 244000062730 Melissa officinalis Species 0.000 description 2
- 235000010654 Melissa officinalis Nutrition 0.000 description 2
- DATAGRPVKZEWHA-YFKPBYRVSA-N N(5)-ethyl-L-glutamine Chemical compound CCNC(=O)CC[C@H]([NH3+])C([O-])=O DATAGRPVKZEWHA-YFKPBYRVSA-N 0.000 description 2
- 206010028980 Neoplasm Diseases 0.000 description 2
- 244000061176 Nicotiana tabacum Species 0.000 description 2
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 2
- 208000008589 Obesity Diseases 0.000 description 2
- 208000021384 Obsessive-Compulsive disease Diseases 0.000 description 2
- 239000004185 Penicillin G procaine Substances 0.000 description 2
- 102000012288 Phosphopyruvate Hydratase Human genes 0.000 description 2
- 108010022181 Phosphopyruvate Hydratase Proteins 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 108020004459 Small interfering RNA Proteins 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 150000007513 acids Chemical class 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000654 additive Substances 0.000 description 2
- 208000017515 adrenocortical insufficiency Diseases 0.000 description 2
- 239000000443 aerosol Substances 0.000 description 2
- VIROVYVQCGLCII-UHFFFAOYSA-N amobarbital Chemical compound CC(C)CCC1(CC)C(=O)NC(=O)NC1=O VIROVYVQCGLCII-UHFFFAOYSA-N 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 230000002238 attenuated effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- WHRVRSCEWKLAHX-LQDWTQKMSA-N benzylpenicillin procaine Chemical compound [H+].CCN(CC)CCOC(=O)C1=CC=C(N)C=C1.N([C@H]1[C@H]2SC([C@@H](N2C1=O)C([O-])=O)(C)C)C(=O)CC1=CC=CC=C1 WHRVRSCEWKLAHX-LQDWTQKMSA-N 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 230000023555 blood coagulation Effects 0.000 description 2
- 201000011510 cancer Diseases 0.000 description 2
- 238000000546 chi-square test Methods 0.000 description 2
- 201000006145 cocaine dependence Diseases 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 238000002648 combination therapy Methods 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 239000003246 corticosteroid Substances 0.000 description 2
- 229960001334 corticosteroids Drugs 0.000 description 2
- 238000007405 data analysis Methods 0.000 description 2
- NIJJYAXOARWZEE-UHFFFAOYSA-N di-n-propyl-acetic acid Natural products CCCC(C(O)=O)CCC NIJJYAXOARWZEE-UHFFFAOYSA-N 0.000 description 2
- 238000003745 diagnosis Methods 0.000 description 2
- 239000003651 drinking water Substances 0.000 description 2
- 235000020188 drinking water Nutrition 0.000 description 2
- 230000000857 drug effect Effects 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000002708 enhancing effect Effects 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 230000037406 food intake Effects 0.000 description 2
- 239000012458 free base Substances 0.000 description 2
- 210000005046 glial fibrillary acidic protein Anatomy 0.000 description 2
- 239000003667 hormone antagonist Substances 0.000 description 2
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 238000002513 implantation Methods 0.000 description 2
- 208000015181 infectious disease Diseases 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 229960001632 labetalol Drugs 0.000 description 2
- 239000008101 lactose Substances 0.000 description 2
- PYZRQGJRPPTADH-UHFFFAOYSA-N lamotrigine Chemical compound NC1=NC(N)=NN=C1C1=CC=CC(Cl)=C1Cl PYZRQGJRPPTADH-UHFFFAOYSA-N 0.000 description 2
- 239000007788 liquid 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
- 238000007726 management method Methods 0.000 description 2
- 235000012054 meals Nutrition 0.000 description 2
- 230000009245 menopause Effects 0.000 description 2
- 229960001797 methadone Drugs 0.000 description 2
- 229960002237 metoprolol Drugs 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 description 2
- VWPOSFSPZNDTMJ-UCWKZMIHSA-N nadolol Chemical compound C1[C@@H](O)[C@@H](O)CC2=C1C=CC=C2OCC(O)CNC(C)(C)C VWPOSFSPZNDTMJ-UCWKZMIHSA-N 0.000 description 2
- 239000002858 neurotransmitter agent Substances 0.000 description 2
- 235000020824 obesity Nutrition 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 230000031868 operant conditioning Effects 0.000 description 2
- 238000007427 paired t-test Methods 0.000 description 2
- 230000037361 pathway Effects 0.000 description 2
- 235000019370 penicillin G procaine Nutrition 0.000 description 2
- 229940056362 penicillin g procaine Drugs 0.000 description 2
- 230000000144 pharmacologic effect Effects 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 239000013612 plasmid Substances 0.000 description 2
- 230000008488 polyadenylation Effects 0.000 description 2
- 239000013641 positive control Substances 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 238000003825 pressing Methods 0.000 description 2
- 229960003712 propranolol Drugs 0.000 description 2
- 238000003127 radioimmunoassay Methods 0.000 description 2
- 238000011552 rat model Methods 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 229920000260 silastic Polymers 0.000 description 2
- 210000000813 small intestine Anatomy 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000021 stimulant Substances 0.000 description 2
- 230000000153 supplemental effect Effects 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- 210000001541 thymus gland Anatomy 0.000 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 description 2
- 229960004394 topiramate Drugs 0.000 description 2
- 231100000331 toxic Toxicity 0.000 description 2
- 230000002588 toxic effect Effects 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- 238000013518 transcription Methods 0.000 description 2
- 230000035897 transcription Effects 0.000 description 2
- 238000013519 translation Methods 0.000 description 2
- 230000032258 transport Effects 0.000 description 2
- 238000011269 treatment regimen Methods 0.000 description 2
- MSRILKIQRXUYCT-UHFFFAOYSA-M valproate semisodium Chemical compound [Na+].CCCC(C(O)=O)CCC.CCCC(C([O-])=O)CCC MSRILKIQRXUYCT-UHFFFAOYSA-M 0.000 description 2
- 229960000604 valproic acid Drugs 0.000 description 2
- 229960005318 vigabatrin Drugs 0.000 description 2
- PJDFLNIOAUIZSL-UHFFFAOYSA-N vigabatrin Chemical compound C=CC(N)CCC(O)=O PJDFLNIOAUIZSL-UHFFFAOYSA-N 0.000 description 2
- UIKROCXWUNQSPJ-VIFPVBQESA-N (-)-cotinine Chemical compound C1CC(=O)N(C)[C@@H]1C1=CC=CN=C1 UIKROCXWUNQSPJ-VIFPVBQESA-N 0.000 description 1
- MJYHSOCPRKVNKH-UHFFFAOYSA-N (8-methyl-8-azabicyclo[3.2.1]octan-3-yl) 3-hydroxy-2-phenylpropanoate;nitric acid Chemical compound O[N+]([O-])=O.CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 MJYHSOCPRKVNKH-UHFFFAOYSA-N 0.000 description 1
- METKIMKYRPQLGS-GFCCVEGCSA-N (R)-atenolol Chemical compound CC(C)NC[C@@H](O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-GFCCVEGCSA-N 0.000 description 1
- KWTSXDURSIMDCE-QMMMGPOBSA-N (S)-amphetamine Chemical compound C[C@H](N)CC1=CC=CC=C1 KWTSXDURSIMDCE-QMMMGPOBSA-N 0.000 description 1
- KFNRJXCQEJIBER-ZCFIWIBFSA-N (S)-gabaculine Chemical compound N[C@H]1CC(C(O)=O)=CC=C1 KFNRJXCQEJIBER-ZCFIWIBFSA-N 0.000 description 1
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 1
- BRIPGNJWPCKDQZ-WXXKFALUSA-N (e)-but-2-enedioic acid;1-[4-(2-methoxyethyl)phenoxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound OC(=O)\C=C\C(O)=O.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1.COCCC1=CC=C(OCC(O)CNC(C)C)C=C1 BRIPGNJWPCKDQZ-WXXKFALUSA-N 0.000 description 1
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-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
- ALEVUYMOJKJJSA-UHFFFAOYSA-N 4-hydroxy-2-propylbenzoic acid Chemical compound CCCC1=CC(O)=CC=C1C(O)=O ALEVUYMOJKJJSA-UHFFFAOYSA-N 0.000 description 1
- SJZRECIVHVDYJC-UHFFFAOYSA-N 4-hydroxybutyric acid Chemical compound OCCCC(O)=O SJZRECIVHVDYJC-UHFFFAOYSA-N 0.000 description 1
- YPOQUAYRZPJZHW-UHFFFAOYSA-N 6-chloro-1,1-dioxo-3,4-dihydro-2h-1$l^{6},2,4-benzothiadiazine-7-sulfonamide;1-(propan-2-ylamino)-3-[4-(2-propan-2-yloxyethoxymethyl)phenoxy]propan-2-ol Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 YPOQUAYRZPJZHW-UHFFFAOYSA-N 0.000 description 1
- 102100033350 ATP-dependent translocase ABCB1 Human genes 0.000 description 1
- 208000007848 Alcoholism Diseases 0.000 description 1
- 235000019489 Almond oil Nutrition 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- KPYSYYIEGFHWSV-UHFFFAOYSA-N Baclofen Chemical compound OC(=O)CC(CN)C1=CC=C(Cl)C=C1 KPYSYYIEGFHWSV-UHFFFAOYSA-N 0.000 description 1
- 229940122226 Benzodiazepine receptor agonist Drugs 0.000 description 1
- 208000020925 Bipolar disease Diseases 0.000 description 1
- 102400000967 Bradykinin Human genes 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- 208000032841 Bulimia Diseases 0.000 description 1
- 206010006550 Bulimia nervosa Diseases 0.000 description 1
- 241000282472 Canis lupus familiaris Species 0.000 description 1
- 244000025254 Cannabis sativa Species 0.000 description 1
- 235000012766 Cannabis sativa ssp. sativa var. sativa Nutrition 0.000 description 1
- 235000012765 Cannabis sativa ssp. sativa var. spontanea Nutrition 0.000 description 1
- 206010007559 Cardiac failure congestive Diseases 0.000 description 1
- 102000000844 Cell Surface Receptors Human genes 0.000 description 1
- 108010001857 Cell Surface Receptors Proteins 0.000 description 1
- 102000020313 Cell-Penetrating Peptides Human genes 0.000 description 1
- 108010051109 Cell-Penetrating Peptides Proteins 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108091026890 Coding region Proteins 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 108020004394 Complementary RNA Proteins 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- UIKROCXWUNQSPJ-UHFFFAOYSA-N Cotinine Natural products C1CC(=O)N(C)C1C1=CC=CN=C1 UIKROCXWUNQSPJ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- 108020004414 DNA Proteins 0.000 description 1
- 101710177611 DNA polymerase II large subunit Proteins 0.000 description 1
- 101710184669 DNA polymerase II small subunit Proteins 0.000 description 1
- 238000001712 DNA sequencing Methods 0.000 description 1
- 206010013654 Drug abuse Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 241000282326 Felis catus Species 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108091006027 G proteins Proteins 0.000 description 1
- 102000003688 G-Protein-Coupled Receptors Human genes 0.000 description 1
- 108090000045 G-Protein-Coupled Receptors Proteins 0.000 description 1
- 102000004300 GABA-A Receptors Human genes 0.000 description 1
- 108090000839 GABA-A Receptors Proteins 0.000 description 1
- 102000030782 GTP binding Human genes 0.000 description 1
- 108091000058 GTP-Binding Proteins 0.000 description 1
- 102100033417 Glucocorticoid receptor Human genes 0.000 description 1
- JMBQKKAJIKAWKF-UHFFFAOYSA-N Glutethimide Chemical compound C=1C=CC=CC=1C1(CC)CCC(=O)NC1=O JMBQKKAJIKAWKF-UHFFFAOYSA-N 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 206010019280 Heart failures Diseases 0.000 description 1
- GVGLGOZIDCSQPN-PVHGPHFFSA-N Heroin Chemical compound O([C@H]1[C@H](C=C[C@H]23)OC(C)=O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4OC(C)=O GVGLGOZIDCSQPN-PVHGPHFFSA-N 0.000 description 1
- 241000282821 Hippopotamus Species 0.000 description 1
- 101000926939 Homo sapiens Glucocorticoid receptor Proteins 0.000 description 1
- 102000003839 Human Proteins Human genes 0.000 description 1
- 108090000144 Human Proteins Proteins 0.000 description 1
- 241000713772 Human immunodeficiency virus 1 Species 0.000 description 1
- 206010062767 Hypophysitis Diseases 0.000 description 1
- 102000017727 Immunoglobulin Variable Region Human genes 0.000 description 1
- 108010067060 Immunoglobulin Variable Region Proteins 0.000 description 1
- UGQMRVRMYYASKQ-KQYNXXCUSA-N Inosine Chemical group O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(O)=C2N=C1 UGQMRVRMYYASKQ-KQYNXXCUSA-N 0.000 description 1
- 229930010555 Inosine Natural products 0.000 description 1
- PIWKPBJCKXDKJR-UHFFFAOYSA-N Isoflurane Chemical compound FC(F)OC(Cl)C(F)(F)F PIWKPBJCKXDKJR-UHFFFAOYSA-N 0.000 description 1
- DATAGRPVKZEWHA-UHFFFAOYSA-N L-gamma-glutamyl-n-ethylamine Natural products CCNC(=O)CCC(N)C(O)=O DATAGRPVKZEWHA-UHFFFAOYSA-N 0.000 description 1
- 229930182816 L-glutamine Natural products 0.000 description 1
- 108091026898 Leader sequence (mRNA) Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 108010047230 Member 1 Subfamily B ATP Binding Cassette Transporter Proteins 0.000 description 1
- JEYCTXHKTXCGPB-UHFFFAOYSA-N Methaqualone Chemical compound CC1=CC=CC=C1N1C(=O)C2=CC=CC=C2N=C1C JEYCTXHKTXCGPB-UHFFFAOYSA-N 0.000 description 1
- DUGOZIWVEXMGBE-UHFFFAOYSA-N Methylphenidate Chemical compound C=1C=CC=CC=1C(C(=O)OC)C1CCCCN1 DUGOZIWVEXMGBE-UHFFFAOYSA-N 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- 208000031888 Mycoses Diseases 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 206010067482 No adverse event Diseases 0.000 description 1
- 108091092724 Noncoding DNA Proteins 0.000 description 1
- 101710163270 Nuclease Proteins 0.000 description 1
- 108091028043 Nucleic acid sequence Proteins 0.000 description 1
- 239000008896 Opium Substances 0.000 description 1
- BRUQQQPBMZOVGD-XFKAJCMBSA-N Oxycodone Chemical compound O=C([C@@H]1O2)CC[C@@]3(O)[C@H]4CC5=CC=C(OC)C2=C5[C@@]13CCN4C BRUQQQPBMZOVGD-XFKAJCMBSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- QGMRQYFBGABWDR-UHFFFAOYSA-M Pentobarbital sodium Chemical compound [Na+].CCCC(C)C1(CC)C(=O)NC(=O)[N-]C1=O QGMRQYFBGABWDR-UHFFFAOYSA-M 0.000 description 1
- 108091093037 Peptide nucleic acid Proteins 0.000 description 1
- LBWQSAZEYIZZCE-SNVBAGLBSA-N Pexacerfont Chemical compound CC1=NN2C(N[C@H](C)CC)=NC(C)=NC2=C1C1=CC=C(OC)N=C1C LBWQSAZEYIZZCE-SNVBAGLBSA-N 0.000 description 1
- RMUCZJUITONUFY-UHFFFAOYSA-N Phenelzine Chemical compound NNCCC1=CC=CC=C1 RMUCZJUITONUFY-UHFFFAOYSA-N 0.000 description 1
- 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 description 1
- 229920005372 Plexiglas® Polymers 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 102000004257 Potassium Channel Human genes 0.000 description 1
- 206010036618 Premenstrual syndrome Diseases 0.000 description 1
- KNAHARQHSZJURB-UHFFFAOYSA-N Propylthiouracile Chemical compound CCCC1=CC(=O)NC(=S)N1 KNAHARQHSZJURB-UHFFFAOYSA-N 0.000 description 1
- 206010037180 Psychiatric symptoms Diseases 0.000 description 1
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
- 101710146873 Receptor-binding protein Proteins 0.000 description 1
- 108091028664 Ribonucleotide Proteins 0.000 description 1
- FTALBRSUTCGOEG-UHFFFAOYSA-N Riluzole Chemical compound C1=C(OC(F)(F)F)C=C2SC(N)=NC2=C1 FTALBRSUTCGOEG-UHFFFAOYSA-N 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 241000632296 Scutellaria lateriflora Species 0.000 description 1
- 108091081021 Sense strand Proteins 0.000 description 1
- 108091027967 Small hairpin RNA Proteins 0.000 description 1
- 206010041250 Social phobia Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 102000004584 Somatomedin Receptors Human genes 0.000 description 1
- 108010017622 Somatomedin Receptors Proteins 0.000 description 1
- 108010049356 Steroid 11-beta-Hydroxylase Proteins 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- 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 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 108030001722 Tentoxilysin Proteins 0.000 description 1
- IUJDSEJGGMCXSG-UHFFFAOYSA-N Thiopental Chemical compound CCCC(C)C1(CC)C(=O)NC(=S)NC1=O IUJDSEJGGMCXSG-UHFFFAOYSA-N 0.000 description 1
- 108091036066 Three prime untranslated region Proteins 0.000 description 1
- 208000031674 Traumatic Acute Stress disease Diseases 0.000 description 1
- 244000126014 Valeriana officinalis Species 0.000 description 1
- 235000013832 Valeriana officinalis Nutrition 0.000 description 1
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 1
- 108010004977 Vasopressins Proteins 0.000 description 1
- 102000002852 Vasopressins Human genes 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 229960002122 acebutolol Drugs 0.000 description 1
- GOEMGAFJFRBGGG-UHFFFAOYSA-N acebutolol Chemical compound CCCC(=O)NC1=CC=C(OCC(O)CNC(C)C)C(C(C)=O)=C1 GOEMGAFJFRBGGG-UHFFFAOYSA-N 0.000 description 1
- 125000000641 acridinyl group Chemical group C1(=CC=CC2=NC3=CC=CC=C3C=C12)* 0.000 description 1
- 230000001154 acute effect Effects 0.000 description 1
- 208000026345 acute stress disease Diseases 0.000 description 1
- 230000002730 additional effect Effects 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001919 adrenal effect Effects 0.000 description 1
- 230000009824 affinity maturation Effects 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003295 alanine group Chemical group N[C@@H](C)C(=O)* 0.000 description 1
- 201000007930 alcohol dependence Diseases 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000008168 almond oil Substances 0.000 description 1
- 229960001301 amobarbital Drugs 0.000 description 1
- 229940042767 amobarbital / secobarbital Drugs 0.000 description 1
- 229940025084 amphetamine Drugs 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 238000003975 animal breeding Methods 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 229940124691 antibody therapeutics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 229960003153 aprobarbital Drugs 0.000 description 1
- UORJNBVJVRLXMQ-UHFFFAOYSA-N aprobarbital Chemical compound C=CCC1(C(C)C)C(=O)NC(=O)NC1=O UORJNBVJVRLXMQ-UHFFFAOYSA-N 0.000 description 1
- 239000008135 aqueous vehicle Substances 0.000 description 1
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 1
- 108010063987 astressin Proteins 0.000 description 1
- HPYIIXJJVYSMCV-MGDXKYBTSA-N astressin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]1C(N[C@@H](C)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@@H](CCCCNC(=O)CC1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)=O)C(C)C)NC(=O)[C@H](N)CC=1C=CC=CC=1)C1=CNC=N1 HPYIIXJJVYSMCV-MGDXKYBTSA-N 0.000 description 1
- 108010025261 astressin B Proteins 0.000 description 1
- BGFHNAZIBICPLD-IXILWOCFSA-N astressin b Chemical compound C([C@@H](C(=O)N[C@](C)(CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)NC1C(N[C@H](CC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCNC(=O)CC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@](C)(CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(N)=O)=O)NC(=O)[C@@H](CC=1C=CC=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(C)=O)C1=CNC=N1 BGFHNAZIBICPLD-IXILWOCFSA-N 0.000 description 1
- 229960002274 atenolol Drugs 0.000 description 1
- METKIMKYRPQLGS-UHFFFAOYSA-N atenolol Chemical compound CC(C)NCC(O)COC1=CC=C(CC(N)=O)C=C1 METKIMKYRPQLGS-UHFFFAOYSA-N 0.000 description 1
- 229960002430 atomoxetine Drugs 0.000 description 1
- VHGCDTVCOLNTBX-QGZVFWFLSA-N atomoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=CC=C1C VHGCDTVCOLNTBX-QGZVFWFLSA-N 0.000 description 1
- 229960000794 baclofen Drugs 0.000 description 1
- 229960002319 barbital Drugs 0.000 description 1
- 229910052788 barium Inorganic materials 0.000 description 1
- DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
- 239000000759 benzodiazepine receptor stimulating agent Substances 0.000 description 1
- DZBUGLKDJFMEHC-UHFFFAOYSA-N benzoquinolinylidene Chemical group C1=CC=CC2=CC3=CC=CC=C3N=C21 DZBUGLKDJFMEHC-UHFFFAOYSA-N 0.000 description 1
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 1
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- CHDPSNLJFOQTRK-UHFFFAOYSA-N betaxolol hydrochloride Chemical compound [Cl-].C1=CC(OCC(O)C[NH2+]C(C)C)=CC=C1CCOCC1CC1 CHDPSNLJFOQTRK-UHFFFAOYSA-N 0.000 description 1
- 230000002146 bilateral effect Effects 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 208000028683 bipolar I disease Diseases 0.000 description 1
- 208000025307 bipolar depression Diseases 0.000 description 1
- 229960002781 bisoprolol Drugs 0.000 description 1
- VHYCDWMUTMEGQY-UHFFFAOYSA-N bisoprolol Chemical compound CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VHYCDWMUTMEGQY-UHFFFAOYSA-N 0.000 description 1
- VMDFASMUILANOL-WXXKFALUSA-N bisoprolol fumarate Chemical compound [H+].[H+].[O-]C(=O)\C=C\C([O-])=O.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1.CC(C)NCC(O)COC1=CC=C(COCCOC(C)C)C=C1 VMDFASMUILANOL-WXXKFALUSA-N 0.000 description 1
- 238000004820 blood count Methods 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 230000003925 brain function Effects 0.000 description 1
- 239000000337 buffer salt Substances 0.000 description 1
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 description 1
- 229960001058 bupropion Drugs 0.000 description 1
- 229940015694 butabarbital Drugs 0.000 description 1
- 229940057317 butisol Drugs 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- FFGPTBGBLSHEPO-UHFFFAOYSA-N carbamazepine Chemical compound C1=CC2=CC=CC=C2N(C(=O)N)C2=CC=CC=C21 FFGPTBGBLSHEPO-UHFFFAOYSA-N 0.000 description 1
- 229960000623 carbamazepine Drugs 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 229960004195 carvedilol Drugs 0.000 description 1
- NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 description 1
- 210000000170 cell membrane Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 230000007248 cellular mechanism Effects 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000002561 chemical irritant Substances 0.000 description 1
- 210000000038 chest Anatomy 0.000 description 1
- RNFNDJAIBTYOQL-UHFFFAOYSA-N chloral hydrate Chemical compound OC(O)C(Cl)(Cl)Cl RNFNDJAIBTYOQL-UHFFFAOYSA-N 0.000 description 1
- 229960002327 chloral hydrate Drugs 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 235000019504 cigarettes Nutrition 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 208000019425 cirrhosis of liver Diseases 0.000 description 1
- 238000009535 clinical urine test Methods 0.000 description 1
- 238000011260 co-administration Methods 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229940000425 combination drug Drugs 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 238000013329 compounding Methods 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000010485 coping Effects 0.000 description 1
- 229940097488 corgard Drugs 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 108010050742 corticotropin releasing hormone (9-41) Proteins 0.000 description 1
- 229950006073 cotinine Drugs 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- 210000000805 cytoplasm Anatomy 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 239000003405 delayed action preparation Substances 0.000 description 1
- 239000003479 dental cement Substances 0.000 description 1
- 238000001784 detoxification Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 229960002069 diamorphine Drugs 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- 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 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- XYYVYLMBEZUESM-UHFFFAOYSA-N dihydrocodeine Natural products C1C(N(CCC234)C)C2C=CC(=O)C3OC2=C4C1=CC=C2OC XYYVYLMBEZUESM-UHFFFAOYSA-N 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 239000002270 dispersing agent Substances 0.000 description 1
- 230000003291 dopaminomimetic effect Effects 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000009977 dual effect Effects 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 208000024732 dysthymic disease Diseases 0.000 description 1
- 239000012636 effector Substances 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002124 endocrine Effects 0.000 description 1
- 210000003372 endocrine gland Anatomy 0.000 description 1
- 229960003745 esmolol Drugs 0.000 description 1
- AQNDDEOPVVGCPG-UHFFFAOYSA-N esmolol Chemical compound COC(=O)CCC1=CC=C(OCC(O)CNC(C)C)C=C1 AQNDDEOPVVGCPG-UHFFFAOYSA-N 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- BEFDCLMNVWHSGT-UHFFFAOYSA-N ethenylcyclopentane Chemical compound C=CC1CCCC1 BEFDCLMNVWHSGT-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- NPUKDXXFDDZOKR-LLVKDONJSA-N etomidate Chemical compound CCOC(=O)C1=CN=CN1[C@H](C)C1=CC=CC=C1 NPUKDXXFDDZOKR-LLVKDONJSA-N 0.000 description 1
- 229960001690 etomidate Drugs 0.000 description 1
- 230000005281 excited state Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000011888 foil Substances 0.000 description 1
- 230000009246 food effect Effects 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000012631 food intake Nutrition 0.000 description 1
- 235000019138 food restriction Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 229960002870 gabapentin Drugs 0.000 description 1
- 229940084457 gabitril Drugs 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007897 gelcap Substances 0.000 description 1
- 208000037870 generalized anxiety Diseases 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229940126013 glucocorticoid receptor antagonist Drugs 0.000 description 1
- 239000003850 glucocorticoid receptor antagonist Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 229960002972 glutethimide Drugs 0.000 description 1
- 230000009931 harmful effect Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000009396 hybridization Methods 0.000 description 1
- 210000004408 hybridoma Anatomy 0.000 description 1
- LLPOLZWFYMWNKH-CMKMFDCUSA-N hydrocodone Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)CC(=O)[C@@H]1OC1=C2C3=CC=C1OC LLPOLZWFYMWNKH-CMKMFDCUSA-N 0.000 description 1
- 229960000240 hydrocodone Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 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 1
- IWBJJCOKGLUQIZ-HQKKAZOISA-N hyperforin Chemical compound OC1=C(CC=C(C)C)C(=O)[C@@]2(CC=C(C)C)C[C@H](CC=C(C)C)[C@](CCC=C(C)C)(C)[C@]1(C(=O)C(C)C)C2=O IWBJJCOKGLUQIZ-HQKKAZOISA-N 0.000 description 1
- QOVWXXKVLJOKNW-UHFFFAOYSA-N hyperforin Natural products CC(C)C(=O)C12CC(CC=C(C)C)(CC(CC=C(C)C)C1CCC=C(C)C)C(=C(CC=C(C)C)C2=O)O QOVWXXKVLJOKNW-UHFFFAOYSA-N 0.000 description 1
- 210000003016 hypothalamus Anatomy 0.000 description 1
- 238000002649 immunization Methods 0.000 description 1
- 230000003053 immunization Effects 0.000 description 1
- 229940027941 immunoglobulin g Drugs 0.000 description 1
- 230000016784 immunoglobulin production Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 229940095990 inderal Drugs 0.000 description 1
- 230000000053 inderal effect Effects 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229960003786 inosine Drugs 0.000 description 1
- 239000000138 intercalating agent Substances 0.000 description 1
- 238000001361 intraarterial administration Methods 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000007913 intrathecal administration Methods 0.000 description 1
- 238000007914 intraventricular administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000003456 ion exchange resin Substances 0.000 description 1
- 229920003303 ion-exchange polymer Polymers 0.000 description 1
- 229910052742 iron Inorganic materials 0.000 description 1
- 230000007794 irritation Effects 0.000 description 1
- 229960002725 isoflurane Drugs 0.000 description 1
- 208000017169 kidney disease Diseases 0.000 description 1
- 230000003907 kidney function Effects 0.000 description 1
- 229940072170 lamictal Drugs 0.000 description 1
- 229960001848 lamotrigine Drugs 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
- 231100000518 lethal Toxicity 0.000 description 1
- 230000001665 lethal effect Effects 0.000 description 1
- 239000002502 liposome Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 208000019423 liver disease Diseases 0.000 description 1
- 230000003908 liver function Effects 0.000 description 1
- 230000033001 locomotion Effects 0.000 description 1
- 229940089504 lopressor Drugs 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 102000006239 metabotropic receptors Human genes 0.000 description 1
- 108020004083 metabotropic receptors Proteins 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- TWXDDNPPQUTEOV-FVGYRXGTSA-N methamphetamine hydrochloride Chemical compound Cl.CN[C@@H](C)CC1=CC=CC=C1 TWXDDNPPQUTEOV-FVGYRXGTSA-N 0.000 description 1
- 229960002803 methaqualone Drugs 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- PIPAJLPNWZMYQA-YVSFHVDLSA-N methylatropine Chemical compound C[N+]1(C)[C@@H]2CC[C@H]1C[C@@H](C2)OC(=O)[C@@H](CO)c3ccccc3 PIPAJLPNWZMYQA-YVSFHVDLSA-N 0.000 description 1
- 229960005096 methylatropine Drugs 0.000 description 1
- 229960001344 methylphenidate 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
- 229960001785 mirtazapine Drugs 0.000 description 1
- RONZAEMNMFQXRA-UHFFFAOYSA-N mirtazapine Chemical compound C1C2=CC=CN=C2N2CCN(C)CC2C2=CC=CC=C21 RONZAEMNMFQXRA-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000009456 molecular mechanism Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 238000002703 mutagenesis Methods 0.000 description 1
- 231100000350 mutagenesis Toxicity 0.000 description 1
- DDSMCPASYQDKFS-UHFFFAOYSA-N n-ethyl-4-[4-(3-fluorophenyl)-3,6-dihydro-2h-pyridin-1-yl]-6-methyl-n-(2-methylsulfanyl-4-propan-2-ylphenyl)pyrimidin-2-amine Chemical compound C=1C=C(C(C)C)C=C(SC)C=1N(CC)C(N=1)=NC(C)=CC=1N(CC=1)CCC=1C1=CC=CC(F)=C1 DDSMCPASYQDKFS-UHFFFAOYSA-N 0.000 description 1
- 229960004255 nadolol Drugs 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229940105631 nembutal Drugs 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 230000001537 neural effect Effects 0.000 description 1
- 210000004498 neuroglial cell Anatomy 0.000 description 1
- 229940072228 neurontin Drugs 0.000 description 1
- 238000002670 nicotine replacement therapy Methods 0.000 description 1
- 108010052671 nicotinic receptor alpha4beta2 Proteins 0.000 description 1
- 239000002687 nonaqueous vehicle Substances 0.000 description 1
- 231100000956 nontoxicity Toxicity 0.000 description 1
- 230000002474 noradrenergic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 0.000 description 1
- 229940124636 opioid drug Drugs 0.000 description 1
- 229960001027 opium Drugs 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000027758 ovulation cycle Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229940124641 pain reliever Drugs 0.000 description 1
- 208000019906 panic disease Diseases 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 229960002035 penbutolol Drugs 0.000 description 1
- KQXKVJAGOJTNJS-HNNXBMFYSA-N penbutolol Chemical compound CC(C)(C)NC[C@H](O)COC1=CC=CC=C1C1CCCC1 KQXKVJAGOJTNJS-HNNXBMFYSA-N 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 229960000964 phenelzine Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- 229960002036 phenytoin Drugs 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 229960002508 pindolol Drugs 0.000 description 1
- PHUTUTUABXHXLW-UHFFFAOYSA-N pindolol Chemical compound CC(C)NCC(O)COC1=CC=CC2=NC=C[C]12 PHUTUTUABXHXLW-UHFFFAOYSA-N 0.000 description 1
- 210000003635 pituitary gland Anatomy 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001296 polysiloxane Polymers 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 230000001242 postsynaptic effect Effects 0.000 description 1
- 108020001213 potassium channel Proteins 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960001233 pregabalin Drugs 0.000 description 1
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 230000037452 priming Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 229960002752 progabide Drugs 0.000 description 1
- IBALRBWGSVJPAP-HEHNFIMWSA-N progabide Chemical compound C=1C(F)=CC=C(O)C=1C(=N/CCCC(=O)N)/C1=CC=C(Cl)C=C1 IBALRBWGSVJPAP-HEHNFIMWSA-N 0.000 description 1
- 229960004134 propofol Drugs 0.000 description 1
- OLBCVFGFOZPWHH-UHFFFAOYSA-N propofol Chemical compound CC(C)C1=CC=CC(C(C)C)=C1O OLBCVFGFOZPWHH-UHFFFAOYSA-N 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 238000001671 psychotherapy Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 230000003362 replicative effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 239000002336 ribonucleotide Substances 0.000 description 1
- 229960004181 riluzole Drugs 0.000 description 1
- 231100000279 safety data Toxicity 0.000 description 1
- KQPKPCNLIDLUMF-UHFFFAOYSA-N secobarbital Chemical compound CCCC(C)C1(CC=C)C(=O)NC(=O)NC1=O KQPKPCNLIDLUMF-UHFFFAOYSA-N 0.000 description 1
- 230000001568 sexual effect Effects 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 230000019491 signal transduction Effects 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 239000004055 small Interfering RNA Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 230000005586 smoking cessation Effects 0.000 description 1
- 230000000391 smoking effect Effects 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 229940079832 sodium starch glycolate Drugs 0.000 description 1
- 239000008109 sodium starch glycolate Substances 0.000 description 1
- 229920003109 sodium starch glycolate Polymers 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 229940075582 sorbic acid Drugs 0.000 description 1
- 235000010199 sorbic acid Nutrition 0.000 description 1
- 239000004334 sorbic acid Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 229960002370 sotalol Drugs 0.000 description 1
- ZBMZVLHSJCTVON-UHFFFAOYSA-N sotalol Chemical compound CC(C)NCC(O)C1=CC=C(NS(C)(=O)=O)C=C1 ZBMZVLHSJCTVON-UHFFFAOYSA-N 0.000 description 1
- 210000004989 spleen cell Anatomy 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000003890 substance P antagonist Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 230000001839 systemic circulation Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000008399 tap water Substances 0.000 description 1
- 235000020679 tap water Nutrition 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 229940090016 tegretol Drugs 0.000 description 1
- 229940015900 tenoretic Drugs 0.000 description 1
- 229940108485 tenormin Drugs 0.000 description 1
- 231100001274 therapeutic index Toxicity 0.000 description 1
- 229960003279 thiopental Drugs 0.000 description 1
- RYYWUUFWQRZTIU-UHFFFAOYSA-K thiophosphate Chemical group [O-]P([O-])([O-])=S RYYWUUFWQRZTIU-UHFFFAOYSA-K 0.000 description 1
- 229960001918 tiagabine Drugs 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229940035305 topamax Drugs 0.000 description 1
- 229940041492 toprol Drugs 0.000 description 1
- LLPOLZWFYMWNKH-UHFFFAOYSA-N trans-dihydrocodeinone Natural products C1C(N(CCC234)C)C2CCC(=O)C3OC2=C4C1=CC=C2OC LLPOLZWFYMWNKH-UHFFFAOYSA-N 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- 238000011830 transgenic mouse model Methods 0.000 description 1
- 230000007723 transport mechanism Effects 0.000 description 1
- 150000003626 triacylglycerols Chemical class 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
- 241000701161 unidentified adenovirus Species 0.000 description 1
- 241001430294 unidentified retrovirus Species 0.000 description 1
- 210000000689 upper leg Anatomy 0.000 description 1
- 238000002562 urinalysis Methods 0.000 description 1
- 235000016788 valerian Nutrition 0.000 description 1
- ZUCZFANFKYSVKF-UHFFFAOYSA-N varenicline hydrochloride Chemical compound Cl.C12=CC3=NC=CN=C3C=C2C2CC1CNC2 ZUCZFANFKYSVKF-UHFFFAOYSA-N 0.000 description 1
- 229960003726 vasopressin Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 239000013603 viral vector Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 229940052204 zebeta Drugs 0.000 description 1
- 229940117978 ziac Drugs 0.000 description 1
- MMSLSKDMIZOHRX-WYDAWZGFSA-N α-helical crf(9-41) Chemical compound OC(=O)C[C@H](N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(N)=O MMSLSKDMIZOHRX-WYDAWZGFSA-N 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
- A61K31/551—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole having two nitrogen atoms, e.g. dilazep
- A61K31/5513—1,4-Benzodiazepines, e.g. diazepam or clozapine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/043—Kallidins; Bradykinins; Related peptides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
-
- 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
-
- 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
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
- A61P25/16—Anti-Parkinson drugs
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/06—Drugs for disorders of the endocrine system of the anterior pituitary hormones, e.g. TSH, ACTH, FSH, LH, PRL, GH
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/38—Drugs for disorders of the endocrine system of the suprarenal hormones
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Biomedical Technology (AREA)
- Psychiatry (AREA)
- Diabetes (AREA)
- Psychology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Hematology (AREA)
- Addiction (AREA)
- Hospice & Palliative Care (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Obesity (AREA)
- Gastroenterology & Hepatology (AREA)
- Child & Adolescent Psychology (AREA)
- Pain & Pain Management (AREA)
- Microbiology (AREA)
- Mycology (AREA)
- Dispersion Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Description
本出願は、2010年6月16日に出願された米国仮特許出願第61/355,482号の出願日の利益を主張する。参照による内容の援用が許可されるすべての法域において、米国仮特許出願第61/355,482号の全内容は、参照することにより本明細書で援用される。
本発明は、国立薬物乱用研究所(National Institute on Drug Abuse)により授与された米国公衆衛生総局基金(United States Public Health Service grant)第DA06013号の下で政府の支持により行われた。政府は本発明についての一定の権利を有する。
本発明は、依存、他の疾患(依存に関連するか又は関連しない精神症状、例えば、不安、心的外傷後ストレス疾患を含む)、及び神経変性病を治療するための組成物と方法とに関する。更に詳しくは本発明は、依存における行動に良い影響を与え、再発リスクを低下させる1又は複数の活性物質を含む医薬組成物を含む。ある実施態様において医薬組成物は、患者に投与した時、血漿コルチゾール濃度を有意に阻害しない用に製剤化され、活性物質は、特に血液脳関門を透過できるように構築される。
薬物のようなある物質への依存、又は賭事のような活動への依存を治療するのに、あるタイプの治療薬を組合せて使用できることを示す研究を、我々は以前行った。これらの以前の研究に基づいて我々は、患者に利益(例えば再発の可能性の低下)をもたらすと思われる併用薬剤療法を記載し、これらの薬剤療法が、HPA軸内の活性を弱める(例えば、HPA軸内内の活性のキュー誘発性上昇を弱めることにより)であろうという仮説を立てた(例えば、米国特許出願公開第2009/0203669号を参照)。既に記載された組成物は、視床下部−下垂体−副腎皮質(HPA)軸を標的とする少なくとも1つの活性成分(「第一」活性物質)、及び前頭前皮質を標的とする少なくとも1つの活性成分(「第二」活性物質)を含むものである。例えば、この組成物は、CRH、ACTH及び/又はコルチゾールの発現又は活性を低下させる第一活性物質と、前頭前皮質内の活性(例えば、阻害性神経伝達物質GABAにより弱められるキュー誘発性活性)を低下させる第二活性物質とを含むであろう。我々の進行中の研究は、この我々が以前記載した治療法を支持しているが、今回我々は、血漿コルチゾール濃度を有意に低下させない医薬組成物を用いることにより、良好な結果が達成されることを示す研究を行った。我々は更に、単独で又は追加の活性物質と組合せて使用できる、メチラポールを含む医薬組成物を考案し;我々は更に、コルチゾール産生性の副腎以外の組織(例えば脳)の有害な活性を選択的に阻害する医薬活性物質を考案し;そして我々は、本明細書に記載の組成物のみでなく、米国特許出願公開第2009/0203669号に既に記載した医薬組成物によっても、追加の症状(例えば神経変性病)を治療できることを示した。
本発明は、種々の組成物と方法とを含み、この組成物は、依存及び本明細書に記載の他の疾患(例えば、不安、鬱病、月経前不機嫌性疾患、統合失調症、及び神経変性病)の治療のための1又は複数の医薬活性物質を含む。我々はまず、本組成物中の活性医薬物質を更に詳細に記載する。
この試験は、45名のコカイン依存者における、コルチゾール合成インヒビターであるメチラポンとベンゾジアゼピンであるオキサゼパムの組合せの、安全性と有効性を評価するために計画した。被験者は、6週間の治療のために、総1日用量が500mgメチラポン/20mgオキサゼパム(低用量)、総1日用量が1500mgメチラポン/20mgオキサゼパム(高用量)、又はプラセボに、ランダムに分類した。結果の尺度は、すべての来院で、尿中のコカイン代謝物BEの定量的測定により決定される、コカイン渇望と関連するコカインの使用の低下である。ランダム化された被験者のうちで、49%が試験を完了した。メチラポンとオキサゼパムの組合せは、充分許容され、コカイン渇望とコカイン使用を低下させる傾向があり、ベースラインスコアについて調整すると、いくつかの時点で有意な低下があった。
メチラポールが動物モデルにおけるコカイン自己投与を低下させる可能性を調べるために、我々は以下の実験を行った。オスの成体ウィスターラットを、交互に変化する15分間中に、食物補給とコカイン自己投与の2時間の複数の交互スケジュール(固定比4)下で、応答するように訓練した。試験前に、ラットを、複数回の食塩水置換と食物枯渇調査に曝露した。試験の日に、行動セッションの開始30分前に、メチラポール(25、50、100、及び150mg/kg、腹腔内)又はビヒクルを用いて、ラットを前処理した。被験体をまず訓練し、0.25mg/kg/注入のコカイン、次に0.125と0.5mg/kg/注入のコカインを用いて試験した。コカイン自己投与は、すべての用量のコカインで用量依存性に低下した。食物維持応答は、最も高い用量のメチラポール以外では、有意に影響を受けなかった。これらのデータは、メチラポールがメチラポンの効果においてある役割を果たすという仮説を支持し、メチラポールがコカイン依存の治療において有用であることを示唆する。
Claims (18)
- メチラポールを含んで成る医薬組成物であって、患者に対して経口又は局所投与するために製剤化されている医薬組成物。
- 第二の医薬活性物質を更に含んで成る、請求項1に記載の医薬組成物。
- 第二の医薬活性物質がGABAの発現又は活性を増大させるか、GABA模倣薬 (mimic)であるか、あるいは前記患者におけるGABA代謝を阻害する、請求項2に記載の医薬組成物。
- メチラポールが、前記患者における血漿コルチゾール濃度を減少させるのに不十分な量の単位剤形で存在している、請求項1〜3のいずれか1項に記載の医薬組成物。
- メチラポールが、血液脳関門を透過する活動を促進する物質と接合している、請求項1〜3のいずれか1項に記載の医薬組成物。
- 脳内のメチラポール濃度を維持するのを助ける流出阻害剤、並びに/あるいはポリエチレングリコール、グリセリン、及びゼラチンのうちの1又は複数を含んで成る賦形剤、を更に含んで成る、請求項1〜3のいずれか1項に記載の医薬組成物。
- 視床下部・下垂体・副腎皮質(HPA)軸を標的とするが、血漿コルチゾールを有意に減少させない第一物質と、前頭前皮質を標的とする第二物質とを含んで成る医薬組成物。
- 前記第一物質が、コルチコトロピン放出ホルモン(CHR)又は副腎皮質刺激ホルモン(ACTH)の発現又は活性を阻害する物質である、請求項7に記載の医薬組成物。
- 前記第一物質がメチラポン(メトピロン(登録商標))、その活性代謝産物、又はケトコナゾール(ニゾラール(登録商標))である、請求項7に記載の医薬組成物。
- 前記第二物質がベンゾジアゼピンである、請求項7〜9のいずれか1項に記載の医薬組成物。
- ベンゾジアゼピンがオキサゼパム又はクロルジアゼポキシドである、請求項10に記載の医薬組成物。
- 前記第一物質が、前記患者における血漿コルチゾール濃度を減少させるのに不十分な量の単位剤形で存在している、請求項7に記載の医薬組成物。
- 前記第一物質及び/又は第二物質が、血液脳関門を透過する活動を促進する部分と接合している、請求項7に記載の医薬組成物。
- 脳内の前記第一物質及び/又は第二物質の濃度を維持するのを助ける流出阻害剤、並びに/あるいはポリエチレングリコール、グリセリン、及びゼラチンのうちの1又は複数を含んで成る賦形剤、を更に含んで成る、請求項7〜9のいずれか1項に記載の医薬組成物。
- HPA軸における異常活性に関連する疾患に罹患している患者を治療する方法であって:
(a)治療を必要とする患者を同定し;そして
(b)当該患者に対し、治療上有効量の請求項1又は7に記載の組成物を投与すること、
を含んで成る、方法。 - 前記疾患が、依存、不安、鬱病、又は統合失調症である、請求項15に記載の方法。
- 神経変性病に罹患している患者を治療する方法であって:
(a)治療を必要とする患者を同定し;そして
(b)当該患者に対し、治療上有効量の請求項1又は7に記載の組成物を投与すること、
を含んで成る、方法。 - 前記神経変性病が、アルツハイマー病、パーキンソン病、ハンチントン病、又は筋萎縮性側索硬化症である、請求項17に記載の方法。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US35548210P | 2010-06-16 | 2010-06-16 | |
US61/355,482 | 2010-06-16 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013515500A Division JP2013528658A (ja) | 2010-06-16 | 2011-06-16 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018168981A Division JP2018188485A (ja) | 2010-06-16 | 2018-09-10 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
Publications (1)
Publication Number | Publication Date |
---|---|
JP2016204394A true JP2016204394A (ja) | 2016-12-08 |
Family
ID=45348860
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013515500A Pending JP2013528658A (ja) | 2010-06-16 | 2011-06-16 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
JP2016177806A Pending JP2016204394A (ja) | 2010-06-16 | 2016-09-12 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
JP2018168981A Pending JP2018188485A (ja) | 2010-06-16 | 2018-09-10 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013515500A Pending JP2013528658A (ja) | 2010-06-16 | 2011-06-16 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2018168981A Pending JP2018188485A (ja) | 2010-06-16 | 2018-09-10 | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 |
Country Status (11)
Country | Link |
---|---|
US (2) | US9078886B2 (ja) |
EP (1) | EP2582375A4 (ja) |
JP (3) | JP2013528658A (ja) |
KR (1) | KR20130135820A (ja) |
CN (2) | CN103037864A (ja) |
AU (2) | AU2011268303A1 (ja) |
BR (1) | BR112012032076A2 (ja) |
CA (1) | CA2802957A1 (ja) |
MX (1) | MX359263B (ja) |
RU (1) | RU2674259C2 (ja) |
WO (1) | WO2011159871A2 (ja) |
Families Citing this family (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA2629199C (en) | 2005-11-10 | 2016-08-09 | Board Of Supervisors Of Louisiana State University & Agricultural & Mechanical College | Compositions and methods for the treatment of addiction and other neuropsychiatry disorders |
BR112012032076A2 (pt) | 2010-06-16 | 2016-09-13 | Univ Louisiana State | composição farmacêutica, e, métodos para tratar um paciente que está sofrendo de um distúrbio e de uma doença neurodegenerativa |
EP3107569A4 (en) | 2014-02-20 | 2018-02-21 | Alder Biopharmaceuticals, Inc. | Anti-acth antibodies and use thereof |
US20180185375A1 (en) * | 2015-06-22 | 2018-07-05 | Embera Neurotherapeutics, Inc. | Compositions and methods for the treatment of substance use disorders, addiction, and psychiatric disorders |
WO2017143034A1 (en) * | 2016-02-16 | 2017-08-24 | Embera Neurotherapeutics, Inc. | Compositions and methods for treating substance abuse disorders |
EP3423063A4 (en) * | 2016-03-04 | 2019-11-06 | Embera Neurotherapeutics, Inc | COMPOSITIONS AND METHODS FOR TREATING SEARCH OR SUBSTANCE ABUSE MISTAKES |
BR112019018700A2 (pt) * | 2017-03-10 | 2020-04-07 | Embera Neurotherapeutics Inc | composições farmacêuticas e seus usos |
US20200360400A1 (en) * | 2017-05-19 | 2020-11-19 | Embera Neurotherapeutics, Inc. | Compositions and methods for the treatment of addiction, psychiatric disorders, and neurodegenerative disease |
KR102081177B1 (ko) | 2017-12-12 | 2020-04-28 | 부산대학교 산학협력단 | 혈관-뇌장벽(Blood-brain barrier) 투과성을 증진시키는 W/O/W형 트리올레인 에멀전을 이용한 약물 전달 플랫폼 |
WO2020028988A1 (en) * | 2018-08-08 | 2020-02-13 | Laviolette Steven Robert | L-theanine and tetrahydrocannabinol formulation |
CN109125338A (zh) * | 2018-08-30 | 2019-01-04 | 泓博元生命科技(深圳)有限公司 | 一种促进神经系统修复的组合物及其制备方法与应用 |
CN109350734A (zh) * | 2018-08-30 | 2019-02-19 | 泓博元生命科技(深圳)有限公司 | 促进神经系统修复的组合物及其制备方法与应用 |
TW202216161A (zh) * | 2020-06-26 | 2022-05-01 | 美商杜瑞克公司 | 氧合膽固醇硫酸酯於治療與人類疱疹病毒第四型(eb病毒)相關之癌和非癌的轉化之用途 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009515899A (ja) * | 2005-11-10 | 2009-04-16 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティー アンド アグリカルチュラル アンド メカニカル カレッジ | 依存症及び他の精神神経疾患の治療のための組成物及び方法 |
Family Cites Families (42)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4942162A (en) | 1982-03-31 | 1990-07-17 | University Of Tennessee Research Corporation | Topical treatment of seborrheic dermatitis with ketoconazole |
US4594329A (en) | 1984-05-14 | 1986-06-10 | The Salk Institute For Biological Studies | CRF analogs |
US4605642A (en) | 1984-02-23 | 1986-08-12 | The Salk Institute For Biological Studies | CRF antagonists |
US4661493A (en) | 1985-03-29 | 1987-04-28 | Pfizer Inc. | Tioconazole and related compounds for control of Herpes simplex virus |
US5016655A (en) | 1986-10-21 | 1991-05-21 | C.A. Blockers, Inc. | Cigarette manufacturing process |
US4814333A (en) | 1987-07-28 | 1989-03-21 | The Trustees Of Dartmouth College | Method for treatment of hypercortisolemic, depressed patients |
US4925844A (en) | 1988-02-09 | 1990-05-15 | Ici Americas Inc. | Antagonizing the pharmacological effects of a benzodiazepine receptor agonist |
US5006528A (en) | 1988-10-31 | 1991-04-09 | Otsuka Pharmaceutical Co., Ltd. | Carbostyril derivatives |
DE3842007A1 (de) | 1988-12-14 | 1990-06-21 | Henkel Kgaa | Fluessiges bis pastoeses, bleichmittelhaltiges waschmittel |
US4974729A (en) | 1989-04-17 | 1990-12-04 | Bristol-Myers Squibb Company | Reminder system for taking medication |
WO1991000906A1 (en) | 1989-07-12 | 1991-01-24 | Genetics Institute, Inc. | Chimeric and transgenic animals capable of producing human antibodies |
US20050090553A1 (en) | 1992-06-30 | 2005-04-28 | Shapiro Howard K. | Compositions and method for treatment of chronic inflammatory diseases |
US6326463B1 (en) | 1994-12-12 | 2001-12-04 | The Salk Institute For Biological Studies | Cyclic CRF agonists |
US6323312B1 (en) | 1994-12-12 | 2001-11-27 | The Salk Institute For Biological Studies | Cyclic CRF antagonist peptides |
US20030211157A1 (en) | 1996-05-06 | 2003-11-13 | Simon David Lew | Semi-sol delivery blend for water soluble molecules |
US5869474A (en) * | 1997-05-16 | 1999-02-09 | Board Of Supervisors Of Louisiana State University And Agricultural And Mechanical College | Low dosage treatment for cocaine craving and withdrawal |
US6476078B2 (en) | 1999-08-11 | 2002-11-05 | Sepracor, Inc. | Methods of using sibutramine metabolites in combination with a phosphodiesterase inhibitor to treat sexual dysfunction |
NZ334627A (en) | 1999-03-12 | 2002-07-26 | Horticulture & Food Res Inst | A therapeutic composition containing a therapeutic agent such as an anthelmintic and an antistress agent such as metyrapone or a nitric oxide promoter for increasing efficacy of therapeutic agents and animal growth |
GB0001449D0 (en) | 2000-01-21 | 2000-03-08 | Cortendo Ab | Compositions |
US6630449B2 (en) | 2000-12-21 | 2003-10-07 | David Wastchak | Method for reducing the effect of nicotine addiction and dependancy |
ATE519493T1 (de) | 2001-06-26 | 2011-08-15 | Univ North Carolina State | Blockierendes peptid für die sekretion von entzündungszellen |
EP1523310A2 (en) | 2002-07-09 | 2005-04-20 | The Scripps Research Institute | Method to inhibit ischemia and reperfusion injury |
KR100503889B1 (ko) * | 2002-07-20 | 2005-07-26 | 한국과학기술연구원 | 옥틸로늄 브로마이드를 함유하는 항암제 흡수 증진제 |
CA2529857A1 (en) | 2002-07-30 | 2004-02-05 | Peter Migaly | Combination therapy for depression, prevention of suicide, and varous medical and psychiatric conditions |
US20040067986A1 (en) | 2002-10-04 | 2004-04-08 | Nathan Sassover | Neuro-degenerative inhibitor, neuro-endocrine modulator, and neuro-cerebral metabolism enhancer |
US20050037983A1 (en) | 2003-03-11 | 2005-02-17 | Timothy Dinan | Compositions and methods for the treatment of depression and other affective disorders |
US20080206138A1 (en) | 2003-08-06 | 2008-08-28 | Ilse Zolle | Radiolabelled Phenylethyl Imidazole Carboxylic Acid Ester Derivatives |
AU2004272437A1 (en) | 2003-09-09 | 2005-03-24 | Ono Pharmaceutical Co., Ltd. | CRF antagonists and heterobicyclic compounds |
US20050203130A1 (en) | 2003-12-02 | 2005-09-15 | Erik Buntinx | Use of D4 and 5-HT2A antagonists, inverse agonists or partial agonists |
JPWO2005061508A1 (ja) | 2003-12-22 | 2007-07-12 | 小野薬品工業株式会社 | 三環式複素環化合物およびその化合物を有効成分とする医薬 |
JP4399593B2 (ja) | 2004-04-01 | 2010-01-20 | 国立大学法人 千葉大学 | インフルエンザ脳症の検査法、及び、ヒト髄液中に発現するタンパク質からなるマーカ、診断薬、診断キット |
JP2009528289A (ja) | 2006-02-27 | 2009-08-06 | ミシャロウ、アレクサンダー | 対抗適応を誘発することにより神経伝達物質系を調節する方法 |
WO2008079868A1 (en) | 2006-12-22 | 2008-07-03 | Drugtech Corporation | Clonidine composition and method of use |
US8318813B2 (en) | 2007-09-13 | 2012-11-27 | Lcs Group, Llc | Method of treating binge eating disorder |
WO2011064769A1 (en) | 2009-11-24 | 2011-06-03 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods and pharmaceutical compositions for the treatment of hot flashes |
CN102711916B (zh) | 2010-01-14 | 2015-09-02 | 诺华股份有限公司 | 肾上腺激素调节剂的用途 |
BR112012032076A2 (pt) | 2010-06-16 | 2016-09-13 | Univ Louisiana State | composição farmacêutica, e, métodos para tratar um paciente que está sofrendo de um distúrbio e de uma doença neurodegenerativa |
US20120237482A1 (en) | 2011-03-18 | 2012-09-20 | Juan Rodriguez | Methods for treatment of neurological disorders by modulation of microglial activation |
US20150278438A1 (en) | 2012-04-23 | 2015-10-01 | MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. | Genetic predictors of response to treatment with crhr1 antagonists |
US20160008375A1 (en) | 2013-03-01 | 2016-01-14 | Sanovel Ilac Sanayi Ve Ticaret A.S. | Pharmaceutical formulations comprising quetiapine and escitalopram |
JP2016523918A (ja) | 2013-06-27 | 2016-08-12 | シーダーズ−サイナイ メディカル センター | 神経変性状態の予防および治療のためのアドレナリン受容体拮抗薬 |
WO2015066344A1 (en) | 2013-11-01 | 2015-05-07 | Arena Pharmaceuticals, Inc. | 5-ht2c receptor agonists and compositions and methods of use |
-
2011
- 2011-06-16 BR BR112012032076A patent/BR112012032076A2/pt not_active Application Discontinuation
- 2011-06-16 WO PCT/US2011/040647 patent/WO2011159871A2/en active Application Filing
- 2011-06-16 CA CA2802957A patent/CA2802957A1/en not_active Abandoned
- 2011-06-16 EP EP11796418.9A patent/EP2582375A4/en not_active Withdrawn
- 2011-06-16 US US13/703,726 patent/US9078886B2/en active Active
- 2011-06-16 KR KR1020137001119A patent/KR20130135820A/ko not_active Application Discontinuation
- 2011-06-16 JP JP2013515500A patent/JP2013528658A/ja active Pending
- 2011-06-16 AU AU2011268303A patent/AU2011268303A1/en not_active Abandoned
- 2011-06-16 CN CN2011800299130A patent/CN103037864A/zh active Pending
- 2011-06-16 CN CN201710832758.5A patent/CN107625769A/zh active Pending
- 2011-06-16 RU RU2013101766A patent/RU2674259C2/ru active
- 2011-06-16 MX MX2012014846A patent/MX359263B/es active IP Right Grant
-
2015
- 2015-06-11 US US14/736,619 patent/US9987286B2/en active Active
-
2016
- 2016-09-12 JP JP2016177806A patent/JP2016204394A/ja active Pending
- 2016-11-24 AU AU2016262733A patent/AU2016262733A1/en not_active Abandoned
-
2018
- 2018-09-10 JP JP2018168981A patent/JP2018188485A/ja active Pending
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2009515899A (ja) * | 2005-11-10 | 2009-04-16 | ボード オブ スーパーバイザーズ オブ ルイジアナ ステイト ユニバーシティー アンド アグリカルチュラル アンド メカニカル カレッジ | 依存症及び他の精神神経疾患の治療のための組成物及び方法 |
Non-Patent Citations (2)
Title |
---|
NEUROSCIENCE2008 ABSTRACT, 2008, 661.4/HH5, JPN6015022261 * |
PHARMACOLOGY, BIOCHEMISTRY AND BEHAVIOR, 2008, VOL.91, P.181-189, vol. Vol.91, JPN6015022265, 2008, pages 181 - 189 * |
Also Published As
Publication number | Publication date |
---|---|
JP2018188485A (ja) | 2018-11-29 |
EP2582375A2 (en) | 2013-04-24 |
WO2011159871A2 (en) | 2011-12-22 |
AU2011268303A1 (en) | 2013-01-24 |
MX2012014846A (es) | 2013-12-16 |
BR112012032076A2 (pt) | 2016-09-13 |
CA2802957A1 (en) | 2011-12-22 |
CN107625769A (zh) | 2018-01-26 |
WO2011159871A8 (en) | 2013-01-31 |
AU2016262733A1 (en) | 2016-12-15 |
KR20130135820A (ko) | 2013-12-11 |
US20130303523A1 (en) | 2013-11-14 |
JP2013528658A (ja) | 2013-07-11 |
MX359263B (es) | 2018-09-20 |
EP2582375A4 (en) | 2013-12-25 |
US9078886B2 (en) | 2015-07-14 |
RU2013101766A (ru) | 2014-07-27 |
WO2011159871A3 (en) | 2012-04-19 |
RU2674259C2 (ru) | 2018-12-06 |
CN103037864A (zh) | 2013-04-10 |
US9987286B2 (en) | 2018-06-05 |
US20160038509A1 (en) | 2016-02-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP2018188485A (ja) | 依存、精神疾患、及び神経変性病の治療のための組成物と方法 | |
US20240033258A1 (en) | Compositions and methods for the treatment of addiction and other neuropsychiatric disorders | |
US20200016134A1 (en) | Compositions and methods for treating substance abuse disorders | |
US20190275058A1 (en) | Compositions and methods for treating addiction or substance use disorders | |
US20200360400A1 (en) | Compositions and methods for the treatment of addiction, psychiatric disorders, and neurodegenerative disease | |
Nakamoto et al. | Nicotine suppresses central post-stroke pain via facilitation of descending noradrenergic neuron through activation of orexinergic neuron | |
Zhao | Mechanisms mediating sex differences in the effects of cocaine |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161012 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20161012 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20170606 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20170905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20171206 |
|
A02 | Decision of refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A02 Effective date: 20180508 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20180910 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A821 Effective date: 20180911 |
|
A911 | Transfer to examiner for re-examination before appeal (zenchi) |
Free format text: JAPANESE INTERMEDIATE CODE: A911 Effective date: 20181019 |
|
A912 | Re-examination (zenchi) completed and case transferred to appeal board |
Free format text: JAPANESE INTERMEDIATE CODE: A912 Effective date: 20181207 |