ZA200306193B - Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders. - Google Patents
Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders. Download PDFInfo
- Publication number
- ZA200306193B ZA200306193B ZA200306193A ZA200306193A ZA200306193B ZA 200306193 B ZA200306193 B ZA 200306193B ZA 200306193 A ZA200306193 A ZA 200306193A ZA 200306193 A ZA200306193 A ZA 200306193A ZA 200306193 B ZA200306193 B ZA 200306193B
- Authority
- ZA
- South Africa
- Prior art keywords
- triene
- methano
- hexahydro
- diazocin
- pyrido
- Prior art date
Links
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 title claims description 80
- 239000000262 estrogen Substances 0.000 title claims description 47
- 208000010877 cognitive disease Diseases 0.000 title claims description 42
- 229960002715 nicotine Drugs 0.000 title claims description 42
- 229930003427 Vitamin E Natural products 0.000 title claims description 40
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 title claims description 40
- SNICXCGAKADSCV-UHFFFAOYSA-N nicotine Natural products CN1CCCC1C1=CC=CN=C1 SNICXCGAKADSCV-UHFFFAOYSA-N 0.000 title claims description 40
- 229940046009 vitamin E Drugs 0.000 title claims description 40
- 235000019165 vitamin E Nutrition 0.000 title claims description 40
- 239000011709 vitamin E Substances 0.000 title claims description 40
- 239000004031 partial agonist Substances 0.000 title claims description 36
- 229940011871 estrogen Drugs 0.000 title claims description 20
- 239000000556 agonist Substances 0.000 title claims description 15
- 238000011282 treatment Methods 0.000 title description 27
- 150000001875 compounds Chemical class 0.000 claims description 90
- 229960003692 gamma aminobutyric acid Drugs 0.000 claims description 71
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 claims description 71
- 229940125425 inverse agonist Drugs 0.000 claims description 62
- 241000124008 Mammalia Species 0.000 claims description 40
- 125000000217 alkyl group Chemical group 0.000 claims description 38
- 150000003839 salts Chemical class 0.000 claims description 36
- SNICXCGAKADSCV-JTQLQIEISA-N (-)-Nicotine Chemical compound CN1CCC[C@H]1C1=CC=CN=C1 SNICXCGAKADSCV-JTQLQIEISA-N 0.000 claims description 34
- 239000008194 pharmaceutical composition Substances 0.000 claims description 24
- 229910052736 halogen Inorganic materials 0.000 claims description 22
- 150000002367 halogens Chemical group 0.000 claims description 21
- 125000004432 carbon atom Chemical group C* 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 18
- -1 benzofuranyi Chemical group 0.000 claims description 17
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 125000002837 carbocyclic group Chemical group 0.000 claims description 13
- 230000027455 binding Effects 0.000 claims description 12
- 125000003282 alkyl amino group Chemical group 0.000 claims description 11
- 239000003937 drug carrier Substances 0.000 claims description 9
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 8
- 239000001257 hydrogen Substances 0.000 claims description 8
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
- 150000005672 tetraenes Chemical class 0.000 claims description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 7
- 239000003814 drug Substances 0.000 claims description 7
- 125000005842 heteroatom Chemical group 0.000 claims description 7
- 229910052760 oxygen Inorganic materials 0.000 claims description 7
- 239000001301 oxygen Substances 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 125000004414 alkyl thio group Chemical group 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 5
- 125000001624 naphthyl group Chemical group 0.000 claims description 5
- 230000003287 optical effect Effects 0.000 claims description 5
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical compound N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 4
- 150000003857 carboxamides Chemical class 0.000 claims description 4
- GQVTUDRXPMPVRX-UHFFFAOYSA-N chembl62858 Chemical compound C1C2CNCC1CN1C2=CC=C(I)C1=O GQVTUDRXPMPVRX-UHFFFAOYSA-N 0.000 claims description 4
- ANJTVLIZGCUXLD-UHFFFAOYSA-N ent-cytisine Natural products C1NCC2CN3C(=O)C=CC=C3C1C2 ANJTVLIZGCUXLD-UHFFFAOYSA-N 0.000 claims description 4
- 125000000623 heterocyclic group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 229940124530 sulfonamide Drugs 0.000 claims description 4
- 150000003456 sulfonamides Chemical class 0.000 claims description 4
- DWDCLEHDNICBMI-UHFFFAOYSA-N 3-bromocytisine Chemical compound C1C2CNCC1CN1C2=CC=C(Br)C1=O DWDCLEHDNICBMI-UHFFFAOYSA-N 0.000 claims description 3
- 125000000477 aza group Chemical group 0.000 claims description 3
- NBGMTBMAENFSAW-UHFFFAOYSA-N chembl64496 Chemical compound C1C2CNCC1CN1C2=CC=C(Cl)C1=O NBGMTBMAENFSAW-UHFFFAOYSA-N 0.000 claims description 3
- 125000005366 cycloalkylthio group Chemical group 0.000 claims description 3
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 3
- 125000004605 1,2,3,4-tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 claims description 2
- YBYIRNPNPLQARY-UHFFFAOYSA-N 1H-indene Natural products C1=CC=C2CC=CC2=C1 YBYIRNPNPLQARY-UHFFFAOYSA-N 0.000 claims description 2
- MYEABNSFVNHLCV-UHFFFAOYSA-N C1C2CNCC1CN1C2=CC=C(C)C1=O Chemical compound C1C2CNCC1CN1C2=CC=C(C)C1=O MYEABNSFVNHLCV-UHFFFAOYSA-N 0.000 claims description 2
- HRVMVUUOSIHXEI-UHFFFAOYSA-N C1C2CNCC1CN1C2=CC=C(CC)C1=O Chemical compound C1C2CNCC1CN1C2=CC=C(CC)C1=O HRVMVUUOSIHXEI-UHFFFAOYSA-N 0.000 claims description 2
- MGQATKFFMYTJKY-UHFFFAOYSA-N C=1C=C2C(C3)CNCC3CN2C(=O)C=1C1=CC=CC=C1 Chemical compound C=1C=C2C(C3)CNCC3CN2C(=O)C=1C1=CC=CC=C1 MGQATKFFMYTJKY-UHFFFAOYSA-N 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 2
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 claims description 2
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 2
- 125000003454 indenyl group Chemical group C1(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- YYFWZOCPJXTWIJ-UHFFFAOYSA-N pyrido[1,2-a][1,5]diazocin-8-one Chemical compound C1=CN=CC=CN2C(=O)C=CC=C21 YYFWZOCPJXTWIJ-UHFFFAOYSA-N 0.000 claims 3
- VHMDFCVLQUZHMQ-UHFFFAOYSA-N 9-vinyl-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one Chemical compound C1C2CNCC1CN1C2=CC=C(C=C)C1=O VHMDFCVLQUZHMQ-UHFFFAOYSA-N 0.000 claims 1
- VIPDMOOFKWHQRH-UHFFFAOYSA-N C1N2C(=O)C(Br)=CC=C2C(C2)CC1CN2CC1=CC=CC=C1 Chemical compound C1N2C(=O)C(Br)=CC=C2C(C2)CC1CN2CC1=CC=CC=C1 VIPDMOOFKWHQRH-UHFFFAOYSA-N 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- YWAKXRMUMFPDSH-UHFFFAOYSA-N pentene Chemical compound CCCC=C YWAKXRMUMFPDSH-UHFFFAOYSA-N 0.000 claims 1
- 229940095743 selective estrogen receptor modulator Drugs 0.000 description 57
- 239000000333 selective estrogen receptor modulator Substances 0.000 description 57
- 238000000034 method Methods 0.000 description 40
- 102000005962 receptors Human genes 0.000 description 32
- 108020003175 receptors Proteins 0.000 description 32
- 239000000203 mixture Substances 0.000 description 25
- 208000024827 Alzheimer disease Diseases 0.000 description 24
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 24
- 230000000694 effects Effects 0.000 description 23
- 238000003556 assay Methods 0.000 description 19
- 208000030886 Traumatic Brain injury Diseases 0.000 description 18
- 239000003795 chemical substances by application Substances 0.000 description 18
- 230000009529 traumatic brain injury Effects 0.000 description 18
- 230000019771 cognition Effects 0.000 description 15
- 238000012360 testing method Methods 0.000 description 15
- 241001465754 Metazoa Species 0.000 description 12
- 201000010099 disease Diseases 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 12
- 208000006096 Attention Deficit Disorder with Hyperactivity Diseases 0.000 description 10
- 208000036864 Attention deficit/hyperactivity disease Diseases 0.000 description 10
- 206010012289 Dementia Diseases 0.000 description 10
- 239000000872 buffer Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 239000012528 membrane Substances 0.000 description 10
- 208000027061 mild cognitive impairment Diseases 0.000 description 10
- 208000030507 AIDS Diseases 0.000 description 9
- 208000019901 Anxiety disease Diseases 0.000 description 9
- 201000010374 Down Syndrome Diseases 0.000 description 9
- 208000023105 Huntington disease Diseases 0.000 description 9
- 208000018737 Parkinson disease Diseases 0.000 description 9
- 208000006011 Stroke Diseases 0.000 description 9
- 206010044688 Trisomy 21 Diseases 0.000 description 9
- 201000004810 Vascular dementia Diseases 0.000 description 9
- 230000007000 age related cognitive decline Effects 0.000 description 9
- 230000036506 anxiety Effects 0.000 description 9
- 208000015802 attention deficit-hyperactivity disease Diseases 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 208000035231 inattentive type attention deficit hyperactivity disease Diseases 0.000 description 9
- 206010027175 memory impairment Diseases 0.000 description 9
- 201000000980 schizophrenia Diseases 0.000 description 9
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 8
- 241000700159 Rattus Species 0.000 description 8
- NKANXQFJJICGDU-QPLCGJKRSA-N Tamoxifen Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=CC(OCCN(C)C)=CC=1)/C1=CC=CC=C1 NKANXQFJJICGDU-QPLCGJKRSA-N 0.000 description 8
- 239000007864 aqueous solution Substances 0.000 description 8
- 230000003920 cognitive function Effects 0.000 description 8
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 8
- GZUITABIAKMVPG-UHFFFAOYSA-N raloxifene Chemical compound C1=CC(O)=CC=C1C1=C(C(=O)C=2C=CC(OCCN3CCCCC3)=CC=2)C2=CC=C(O)C=C2S1 GZUITABIAKMVPG-UHFFFAOYSA-N 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 239000003981 vehicle Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 241000282412 Homo Species 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000007983 Tris buffer Substances 0.000 description 6
- 230000002378 acidificating effect Effects 0.000 description 6
- 238000007796 conventional method Methods 0.000 description 6
- 229940079593 drug Drugs 0.000 description 6
- 229960005309 estradiol Drugs 0.000 description 6
- 239000002834 estrogen receptor modulator Substances 0.000 description 6
- 239000008188 pellet Substances 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 125000002947 alkylene group Chemical group 0.000 description 5
- 239000012736 aqueous medium Substances 0.000 description 5
- 210000004556 brain Anatomy 0.000 description 5
- 239000003085 diluting agent Substances 0.000 description 5
- 230000002708 enhancing effect Effects 0.000 description 5
- 125000001072 heteroaryl group Chemical group 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- ZQZFYGIXNQKOAV-OCEACIFDSA-N Droloxifene Chemical compound C=1C=CC=CC=1C(/CC)=C(C=1C=C(O)C=CC=1)\C1=CC=C(OCCN(C)C)C=C1 ZQZFYGIXNQKOAV-OCEACIFDSA-N 0.000 description 4
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 4
- 239000012131 assay buffer Substances 0.000 description 4
- 238000005119 centrifugation Methods 0.000 description 4
- 230000008859 change Effects 0.000 description 4
- 230000001149 cognitive effect Effects 0.000 description 4
- 229960003638 dopamine Drugs 0.000 description 4
- 229950004203 droloxifene Drugs 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 229940085363 evista Drugs 0.000 description 4
- 235000013305 food Nutrition 0.000 description 4
- 238000004108 freeze drying Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 229960002367 lasofoxifene Drugs 0.000 description 4
- GXESHMAMLJKROZ-IAPPQJPRSA-N lasofoxifene Chemical compound C1([C@@H]2[C@@H](C3=CC=C(C=C3CC2)O)C=2C=CC(OCCN3CCCC3)=CC=2)=CC=CC=C1 GXESHMAMLJKROZ-IAPPQJPRSA-N 0.000 description 4
- 231100000252 nontoxic Toxicity 0.000 description 4
- 230000003000 nontoxic effect Effects 0.000 description 4
- 210000000287 oocyte Anatomy 0.000 description 4
- 238000001556 precipitation Methods 0.000 description 4
- 239000000651 prodrug Substances 0.000 description 4
- 229940002612 prodrug Drugs 0.000 description 4
- 229960004622 raloxifene Drugs 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 239000006228 supernatant Substances 0.000 description 4
- 229960001603 tamoxifen Drugs 0.000 description 4
- 238000012549 training Methods 0.000 description 4
- ANJTVLIZGCUXLD-BDAKNGLRSA-N (-)-Cytisine Natural products C1NC[C@@H]2CN3C(=O)C=CC=C3[C@H]1C2 ANJTVLIZGCUXLD-BDAKNGLRSA-N 0.000 description 3
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 108091026890 Coding region Proteins 0.000 description 3
- YWHLKYXPLRWGSE-UHFFFAOYSA-N Dimethyl trisulfide Chemical compound CSSSC YWHLKYXPLRWGSE-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- 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 3
- 239000004480 active ingredient Substances 0.000 description 3
- 239000003610 charcoal Substances 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- ANJTVLIZGCUXLD-DTWKUNHWSA-N cytisine Chemical compound C1NC[C@H]2CN3C(=O)C=CC=C3[C@@H]1C2 ANJTVLIZGCUXLD-DTWKUNHWSA-N 0.000 description 3
- 229940027564 cytisine Drugs 0.000 description 3
- 229930017327 cytisine Natural products 0.000 description 3
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 229930182833 estradiol Natural products 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 239000003446 ligand Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 230000009871 nonspecific binding Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 230000004962 physiological condition Effects 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 238000007920 subcutaneous administration Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 231100001274 therapeutic index Toxicity 0.000 description 3
- DUDCRNHOLUWPDX-UHFFFAOYSA-N 1,8-naphthyridine-3-carboxamide Chemical compound N1=CC=CC2=CC(C(=O)N)=CN=C21 DUDCRNHOLUWPDX-UHFFFAOYSA-N 0.000 description 2
- CFFZDZCDUFSOFZ-UHFFFAOYSA-N 3,4-Dihydroxy-phenylacetic acid Chemical compound OC(=O)CC1=CC=C(O)C(O)=C1 CFFZDZCDUFSOFZ-UHFFFAOYSA-N 0.000 description 2
- 208000014644 Brain disease Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282693 Cercopithecidae Species 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 206010052804 Drug tolerance Diseases 0.000 description 2
- 102000019315 Nicotinic acetylcholine receptors Human genes 0.000 description 2
- 108050006807 Nicotinic acetylcholine receptors Proteins 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 229930006000 Sucrose Natural products 0.000 description 2
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000000338 anxiogenic effect Effects 0.000 description 2
- 230000003542 behavioural effect Effects 0.000 description 2
- 238000004364 calculation method Methods 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 150000001768 cations Chemical class 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 238000010367 cloning Methods 0.000 description 2
- 230000007278 cognition impairment Effects 0.000 description 2
- 239000002475 cognitive enhancer Substances 0.000 description 2
- 230000003412 degenerative effect Effects 0.000 description 2
- 230000003111 delayed effect Effects 0.000 description 2
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 2
- 230000000763 evoking effect Effects 0.000 description 2
- 239000000284 extract Substances 0.000 description 2
- OFBIFZUFASYYRE-UHFFFAOYSA-N flumazenil Chemical compound C1N(C)C(=O)C2=CC(F)=CC=C2N2C=NC(C(=O)OCC)=C21 OFBIFZUFASYYRE-UHFFFAOYSA-N 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- 230000026781 habituation Effects 0.000 description 2
- 150000004677 hydrates Chemical class 0.000 description 2
- 125000002883 imidazolyl group Chemical group 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- 238000001990 intravenous administration Methods 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
- 108020004999 messenger RNA Proteins 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 125000002971 oxazolyl group Chemical group 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 230000000216 proconvulsive effect Effects 0.000 description 2
- 230000000750 progressive effect Effects 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000000159 protein binding assay Methods 0.000 description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 2
- 238000001525 receptor binding assay Methods 0.000 description 2
- 230000002787 reinforcement Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000003757 reverse transcription PCR Methods 0.000 description 2
- 238000011808 rodent model Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000005720 sucrose Substances 0.000 description 2
- 229910052717 sulfur Inorganic materials 0.000 description 2
- 239000011593 sulfur Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- 125000001544 thienyl group Chemical group 0.000 description 2
- IGRXMNYYQGKFCK-UHFFFAOYSA-N trideca-2,4,6-triene Chemical compound CCCCCCC=CC=CC=CC IGRXMNYYQGKFCK-UHFFFAOYSA-N 0.000 description 2
- 125000005925 3-methylpentyloxy group Chemical group 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- UCDBLYHPJMMFMY-UHFFFAOYSA-N 8-bromoquinoline-4-carbonitrile Chemical compound C1=CN=C2C(Br)=CC=CC2=C1C#N UCDBLYHPJMMFMY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 1
- 208000000044 Amnesia Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- ZUXXFRXUPFGGPW-UHFFFAOYSA-N C12=CC=C(Br)C(=O)N2CC2CN(C)CC1C2 Chemical compound C12=CC=C(Br)C(=O)N2CC2CN(C)CC1C2 ZUXXFRXUPFGGPW-UHFFFAOYSA-N 0.000 description 1
- HYHCJHBDDKMCTD-UHFFFAOYSA-N C1C2CNCC1CN1C2=CC=C(F)C1=O Chemical compound C1C2CNCC1CN1C2=CC=C(F)C1=O HYHCJHBDDKMCTD-UHFFFAOYSA-N 0.000 description 1
- AMUBSCCNOIMNNS-UHFFFAOYSA-N C1N2C(=O)C(Cl)=CC=C2C(C2)CC1CN2CC1=CC=CC=C1 Chemical compound C1N2C(=O)C(Cl)=CC=C2C(C2)CC1CN2CC1=CC=CC=C1 AMUBSCCNOIMNNS-UHFFFAOYSA-N 0.000 description 1
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
- 108091006146 Channels Proteins 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 238000001061 Dunnett's test Methods 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 102000005915 GABA Receptors Human genes 0.000 description 1
- 108010005551 GABA Receptors Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 206010021033 Hypomenorrhoea Diseases 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 101710128836 Large T antigen Proteins 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- GDBQQVLCIARPGH-UHFFFAOYSA-N Leupeptin Natural products CC(C)CC(NC(C)=O)C(=O)NC(CC(C)C)C(=O)NC(C=O)CCCN=C(N)N GDBQQVLCIARPGH-UHFFFAOYSA-N 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 102000018697 Membrane Proteins Human genes 0.000 description 1
- 108010052285 Membrane Proteins Proteins 0.000 description 1
- 208000027382 Mental deterioration Diseases 0.000 description 1
- 206010027374 Mental impairment Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000023146 Pre-existing disease Diseases 0.000 description 1
- 241000288906 Primates Species 0.000 description 1
- 241000283984 Rodentia Species 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 241000269368 Xenopus laevis Species 0.000 description 1
- DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
- 150000001241 acetals Chemical class 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 125000004423 acyloxy group Chemical group 0.000 description 1
- 150000007854 aminals Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 150000001450 anions Chemical class 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 230000003078 antioxidant effect Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 230000000949 anxiolytic effect Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 1
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 238000004166 bioassay Methods 0.000 description 1
- 239000004305 biphenyl Substances 0.000 description 1
- 235000010290 biphenyl Nutrition 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000005388 borosilicate glass Substances 0.000 description 1
- 210000005013 brain tissue Anatomy 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000011575 calcium Substances 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 239000001506 calcium phosphate Substances 0.000 description 1
- 229910000389 calcium phosphate Inorganic materials 0.000 description 1
- 235000011010 calcium phosphates Nutrition 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000004296 chiral HPLC Methods 0.000 description 1
- 210000002932 cholinergic neuron Anatomy 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000037411 cognitive enhancing Effects 0.000 description 1
- 230000003931 cognitive performance Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 210000005257 cortical tissue Anatomy 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000000 cycloalkoxy group Chemical group 0.000 description 1
- 125000005112 cycloalkylalkoxy group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000007405 data analysis Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000000994 depressogenic effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 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
- 229960003529 diazepam Drugs 0.000 description 1
- 235000005911 diet Nutrition 0.000 description 1
- 230000037213 diet Effects 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000000890 drug combination Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 238000003255 drug test Methods 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 102000015694 estrogen receptors Human genes 0.000 description 1
- 108010038795 estrogen receptors Proteins 0.000 description 1
- 238000009164 estrogen replacement therapy Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 239000013604 expression vector Substances 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960004381 flumazenil Drugs 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 238000002825 functional assay Methods 0.000 description 1
- 238000003304 gavage Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000003365 glass fiber Substances 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000007928 intraperitoneal injection Substances 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- GDBQQVLCIARPGH-ULQDDVLXSA-N leupeptin Chemical compound CC(C)C[C@H](NC(C)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C=O)CCCN=C(N)N GDBQQVLCIARPGH-ULQDDVLXSA-N 0.000 description 1
- 108010052968 leupeptin Proteins 0.000 description 1
- 231100000863 loss of memory Toxicity 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 210000004962 mammalian cell Anatomy 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000007595 memory recall Effects 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004593 naphthyridinyl group Chemical group N1=C(C=CC2=CC=CN=C12)* 0.000 description 1
- 230000000324 neuroprotective effect Effects 0.000 description 1
- 210000001009 nucleus accumben Anatomy 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 238000002638 palliative care Methods 0.000 description 1
- 239000006201 parenteral dosage form Substances 0.000 description 1
- 239000003182 parenteral nutrition solution Substances 0.000 description 1
- 235000021400 peanut butter Nutrition 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000005561 phenanthryl group Chemical group 0.000 description 1
- 125000003356 phenylsulfanyl group Chemical group [*]SC1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 239000006187 pill Substances 0.000 description 1
- 230000001817 pituitary effect Effects 0.000 description 1
- 239000013612 plasmid Substances 0.000 description 1
- 239000004033 plastic Substances 0.000 description 1
- 229920003023 plastic Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000003449 preventive effect Effects 0.000 description 1
- 150000003141 primary amines Chemical class 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000004129 prosencephalon Anatomy 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 239000002287 radioligand Substances 0.000 description 1
- 230000010076 replication Effects 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 238000013222 sprague-dawley male rat Methods 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 238000012289 standard assay Methods 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000003270 steroid hormone Substances 0.000 description 1
- 102000005969 steroid hormone receptors Human genes 0.000 description 1
- 108020003113 steroid hormone receptors Proteins 0.000 description 1
- 239000007929 subcutaneous injection Substances 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 210000001550 testis Anatomy 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 239000006211 transdermal dosage form Substances 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- QORWJWZARLRLPR-UHFFFAOYSA-H tricalcium bis(phosphate) Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O QORWJWZARLRLPR-UHFFFAOYSA-H 0.000 description 1
- 230000007306 turnover Effects 0.000 description 1
- 238000003260 vortexing Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000012130 whole-cell lysate Substances 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
-
- 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
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
- A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline
- A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
- A61K31/355—Tocopherols, e.g. vitamin E
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/14—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
- A61P25/22—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
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
- A61P31/18—Antivirals for RNA viruses for HIV
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Neurosurgery (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Virology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Urology & Nephrology (AREA)
- Pain & Pain Management (AREA)
- Vascular Medicine (AREA)
- AIDS & HIV (AREA)
- Tropical Medicine & Parasitology (AREA)
- Molecular Biology (AREA)
- Cardiology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Hospice & Palliative Care (AREA)
- Heart & Thoracic Surgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27256601P | 2001-03-01 | 2001-03-01 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200306193B true ZA200306193B (en) | 2004-08-11 |
Family
ID=23040351
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200306193A ZA200306193B (en) | 2001-03-01 | 2003-08-11 | Use of GABAA inverse agonists in combination with nicotine receptor partial agonists, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders. |
Country Status (33)
| Country | Link |
|---|---|
| US (2) | US20020193360A1 (hu) |
| EP (1) | EP1363606A1 (hu) |
| JP (1) | JP2004527500A (hu) |
| KR (1) | KR20030076717A (hu) |
| CN (1) | CN1494422A (hu) |
| AP (1) | AP2002002465A0 (hu) |
| AR (1) | AR033425A1 (hu) |
| BG (1) | BG108131A (hu) |
| BR (1) | BR0207802A (hu) |
| CA (1) | CA2439581A1 (hu) |
| CR (1) | CR7059A (hu) |
| CZ (1) | CZ20032338A3 (hu) |
| DO (1) | DOP2002000345A (hu) |
| EA (1) | EA200300854A1 (hu) |
| EC (1) | ECSP034759A (hu) |
| EE (1) | EE200300422A (hu) |
| GT (1) | GT200200039A (hu) |
| HU (1) | HUP0303448A3 (hu) |
| IL (1) | IL157465A0 (hu) |
| IS (1) | IS6905A (hu) |
| MA (1) | MA26999A1 (hu) |
| MX (1) | MXPA03007834A (hu) |
| NO (1) | NO20033821L (hu) |
| NZ (1) | NZ527397A (hu) |
| OA (1) | OA12554A (hu) |
| PA (1) | PA8540701A1 (hu) |
| PE (1) | PE20020927A1 (hu) |
| PL (1) | PL364081A1 (hu) |
| SK (1) | SK10752003A3 (hu) |
| TN (1) | TNSN02018A1 (hu) |
| UY (1) | UY27188A1 (hu) |
| WO (1) | WO2002069948A1 (hu) |
| ZA (1) | ZA200306193B (hu) |
Families Citing this family (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6825229B2 (en) | 2002-03-07 | 2004-11-30 | Blanchette Rockefeller Neurosciences Institute | Methods for Alzheimer's Disease treatment and cognitive enhancement |
| US20080004332A1 (en) * | 2002-03-07 | 2008-01-03 | Alkon Daniel L | Methods for alzheimer's disease treatment and cognitive enhancement |
| US20050065205A1 (en) * | 2002-03-07 | 2005-03-24 | Daniel Alkon | Methods for Alzheimer's disease treatment and cognitive enhance |
| WO2005000806A2 (en) | 2003-06-10 | 2005-01-06 | Georgetown University | Ligands for nicotinic acetylcholine receptors, and methods of making and using them |
| TW200538181A (en) | 2004-05-18 | 2005-12-01 | Brni Neurosciences Inst | Treatment of depressive disorders |
| US8510055B2 (en) | 2005-08-03 | 2013-08-13 | The Johns Hopkins University | Methods for characterizing and treating cognitive impairment in aging and disease |
| WO2007019312A2 (en) * | 2005-08-03 | 2007-02-15 | The Johns Hopkins University | Methods for characterizing and treating cognitive impairment in aging and disease |
| CA2935516A1 (en) * | 2006-05-22 | 2007-12-06 | The Board Of Trustees Of The Leland Stanford Junior University | Pharmacological treatment of cognitive impairment |
| WO2008046135A1 (en) | 2006-10-16 | 2008-04-24 | Bionomics Limited | Novel anxiolytic compounds |
| AU2013202426B2 (en) * | 2006-10-16 | 2015-08-06 | Bionomics Limited | Novel anxiolytic compounds |
| US10954231B2 (en) | 2006-10-16 | 2021-03-23 | Bionomics Limited | Anxiolytic compounds |
| KR20090119894A (ko) | 2007-02-09 | 2009-11-20 | 블랜체트 록펠러 뉴로사이언시즈 인스티튜트 | 두부 외상-유도된 기억 장애 및 뇌 손상에 대한 브리오스타틴, 브리오로그 및 기타 관련 물질의 치료학적 효과 |
| CA2709774C (en) * | 2008-05-22 | 2012-10-02 | Teva Pharmaceutical Industries Ltd. | Varenicline tosylate, an intermediate in the preparation process of varenicline l-tartrate |
| WO2009155403A2 (en) * | 2008-06-19 | 2009-12-23 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation of varenicline and intermediates thereof |
| US20100010221A1 (en) * | 2008-07-10 | 2010-01-14 | Revital Lifshitz-Liron | Processes for purifying varenicline l-tartrate salt and preparing crystalline forms of varenicline l-tartrate salt |
| US10206921B2 (en) * | 2009-06-03 | 2019-02-19 | The Regents Of The University Of California | Methods and compositions for treating a subject for central nervous system (CNS) injury |
| US8178537B2 (en) * | 2009-06-22 | 2012-05-15 | Teva Pharmaceutical Industries Ltd. | Solid state forms of varenicline salts and processes for preparation thereof |
| WO2012068161A1 (en) | 2010-11-15 | 2012-05-24 | Agenebio, Inc. | Pyridazine derivatives, compositions and methods for treating cognitive impairment |
| CN103502219A (zh) | 2011-03-02 | 2014-01-08 | 生态学有限公司 | 作为治疗剂的新型小分子 |
| EP2680842A4 (en) * | 2011-03-02 | 2014-10-29 | Bionomics Ltd | METHOD FOR THE TREATMENT OF A DISEASE OR A SENSE OF THE CENTRAL NERVOUS SYSTEM |
| JP6055817B2 (ja) | 2011-05-12 | 2016-12-27 | バイオノミックス リミテッド | ナフチリジンの調製方法 |
| CN112409363B (zh) | 2013-12-20 | 2023-11-14 | 艾吉因生物股份有限公司 | 用于治疗认知损害的苯并二氮杂䓬衍生物、组合物和方法 |
| MX2017015752A (es) | 2015-06-19 | 2018-04-13 | Agenebio Inc | Derivados de benzodiazepina, composiciones y metodos para tratar deterioro cognitivo. |
| BR112019012821A2 (pt) | 2016-12-19 | 2019-11-26 | Agenebio Inc | derivados de benzodiazepina, composições e métodos para o tratamento do comprometimento cognitivo |
| MX2020013927A (es) | 2018-06-19 | 2021-03-02 | Agenebio Inc | Derivados de benzodiazepina, composiciones y metodos para tratar el deterioro cognitivo. |
| CN116008442B (zh) * | 2023-03-27 | 2023-06-30 | 上海赛默罗生物科技有限公司 | α5-GABAA受体调节剂的合成中间体的杂质检测方法 |
| CN116077459B (zh) * | 2023-04-10 | 2023-07-07 | 上海赛默罗生物科技有限公司 | α5-GABAA受体调节剂的胶囊剂及其制备方法 |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2001514181A (ja) * | 1997-08-25 | 2001-09-11 | ニューロゲン コーポレイション | Ｇａｂａ脳レセプタリガンドとしての置換４−オキソ−ナフチリジン−３−カルボキサミド |
| US6448246B1 (en) * | 1999-05-25 | 2002-09-10 | Neurogen Corporation | Substituted 4H-1,4-benzothiazine-2-carboxamide: GABA brain receptor ligands |
-
2002
- 2002-02-20 WO PCT/IB2002/000515 patent/WO2002069948A1/en not_active Application Discontinuation
- 2002-02-20 CA CA002439581A patent/CA2439581A1/en not_active Abandoned
- 2002-02-20 JP JP2002569125A patent/JP2004527500A/ja active Pending
- 2002-02-20 EE EEP200300422A patent/EE200300422A/xx unknown
- 2002-02-20 CZ CZ20032338A patent/CZ20032338A3/cs unknown
- 2002-02-20 OA OA1200300213A patent/OA12554A/en unknown
- 2002-02-20 NZ NZ527397A patent/NZ527397A/en unknown
- 2002-02-20 PL PL02364081A patent/PL364081A1/xx not_active Application Discontinuation
- 2002-02-20 CN CNA028058046A patent/CN1494422A/zh active Pending
- 2002-02-20 BR BR0207802-3A patent/BR0207802A/pt not_active IP Right Cessation
- 2002-02-20 EP EP02700509A patent/EP1363606A1/en not_active Withdrawn
- 2002-02-20 EA EA200300854A patent/EA200300854A1/ru unknown
- 2002-02-20 KR KR10-2003-7011366A patent/KR20030076717A/ko not_active Application Discontinuation
- 2002-02-20 SK SK1075-2003A patent/SK10752003A3/sk not_active Application Discontinuation
- 2002-02-20 HU HU0303448A patent/HUP0303448A3/hu unknown
- 2002-02-20 MX MXPA03007834A patent/MXPA03007834A/es unknown
- 2002-02-20 IL IL15746502A patent/IL157465A0/xx unknown
- 2002-02-26 US US10/083,743 patent/US20020193360A1/en not_active Abandoned
- 2002-02-26 DO DO2002000345A patent/DOP2002000345A/es unknown
- 2002-02-26 PE PE2002000157A patent/PE20020927A1/es not_active Application Discontinuation
- 2002-02-27 UY UY27188A patent/UY27188A1/es not_active Application Discontinuation
- 2002-02-27 AR ARP020100693A patent/AR033425A1/es not_active Application Discontinuation
- 2002-02-27 GT GT200200039A patent/GT200200039A/es unknown
- 2002-02-28 TN TNTNSN02018A patent/TNSN02018A1/fr unknown
- 2002-02-28 PA PA20028540701A patent/PA8540701A1/es unknown
- 2002-02-28 AP APAP/P/2002/002465A patent/AP2002002465A0/en unknown
-
2003
- 2003-08-07 IS IS6905A patent/IS6905A/is unknown
- 2003-08-11 ZA ZA200306193A patent/ZA200306193B/en unknown
- 2003-08-19 MA MA27286A patent/MA26999A1/fr unknown
- 2003-08-25 BG BG108131A patent/BG108131A/xx unknown
- 2003-08-25 CR CR7059A patent/CR7059A/es not_active Application Discontinuation
- 2003-08-28 NO NO20033821A patent/NO20033821L/no not_active Application Discontinuation
- 2003-09-01 EC EC2003004759A patent/ECSP034759A/es unknown
- 2003-12-02 US US10/727,934 patent/US20040082555A1/en not_active Abandoned
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20040082555A1 (en) | Use of gaba, inverse agonists in combination with nicotine receptor partial agonist, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders | |
| Nguyen et al. | Dextromethorphan: An update on its utility for neurological and neuropsychiatric disorders | |
| US20030130303A1 (en) | Pharmaceutical composition and method of treatment of diseases of cognitive dysfunction in a mammal | |
| CA3002544C (en) | 5-ht2c receptor agonists and compositions and methods of use | |
| ZA200207996B (en) | A pharmaceutical composition for treatment of acute, chronic pain and/or neuropathic pain and migraines. | |
| JP2004511512A (ja) | 認識障害の治療のためのアセチルコリンエステラーゼ阻害薬およびｇａｂａａ反作用薬の組合せ使用 | |
| Fritze | The adrenergic-cholinergic imbalance hypothesis of depression: a review and a perspective | |
| CN109952301B (zh) | 5-ht2c受体激动剂和组合物及使用方法 | |
| JP2018519251A5 (hu) | ||
| JP6789578B2 (ja) | ５−ｈｔ２ｃ受容体アゴニストおよび組成物、ならびに使用方法 | |
| US20040220184A1 (en) | Pharmaceutical composition for the treatment of attention deficit hyperactivity disorder (ADHD) | |
| JP6433482B2 (ja) | 認知機能を改善するための方法および組成物 | |
| JP2022064908A (ja) | Ｌ－４－クロロキヌレニンの治療的使用 | |
| US20110034565A1 (en) | Psycho-pharmaceuticals | |
| KR20080105105A (ko) | 인지 장애 및 기타 장애의 치료방법 | |
| KR20200133259A (ko) | Kv7 채널 활성화제 조성물 및 이의 사용 방법 | |
| TW202308634A (zh) | 使用sGC刺激劑之CNS疾病治療 | |
| KR20230096003A (ko) | 만성 ssri 레지멘 후 실로시빈에 대한 민감도를 증가시키기 위한 벤조디아제핀의 사용 | |
| AU2002233585A1 (en) | Use of GABAA inverse agonists in combination with nicotine receptor partial agonisits, estrogen, selective estrogen modulators, or vitamin E for the treatment of cognitive disorders | |
| WO2024039886A1 (en) | Benzazepine derivatives, compositions, and methods for treating cognitive impairment | |
| NZ739883B2 (en) | 5-ht2c receptor agonists and compositions and methods of use | |
| NZ737412B2 (en) | 5-ht2c receptor agonists and compositions and methods of use |