CA2719824A1 - Methods and compositions for treating schizophrenia using antipsychotic combination therapy - Google Patents
Methods and compositions for treating schizophrenia using antipsychotic combination therapy Download PDFInfo
- Publication number
- CA2719824A1 CA2719824A1 CA2719824A CA2719824A CA2719824A1 CA 2719824 A1 CA2719824 A1 CA 2719824A1 CA 2719824 A CA2719824 A CA 2719824A CA 2719824 A CA2719824 A CA 2719824A CA 2719824 A1 CA2719824 A1 CA 2719824A1
- Authority
- CA
- Canada
- Prior art keywords
- antipsychotic
- schizophrenia
- dimebon
- risperidone
- combination therapy
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- 230000000561 anti-psychotic effect Effects 0.000 title claims abstract description 153
- 201000000980 schizophrenia Diseases 0.000 title claims abstract description 144
- 238000002648 combination therapy Methods 0.000 title claims abstract description 132
- 238000000034 method Methods 0.000 title claims abstract description 91
- 239000000203 mixture Substances 0.000 title claims description 35
- JNODQFNWMXFMEV-UHFFFAOYSA-N latrepirdine Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 JNODQFNWMXFMEV-UHFFFAOYSA-N 0.000 claims abstract description 106
- 238000011161 development Methods 0.000 claims abstract description 33
- 239000003693 atypical antipsychotic agent Substances 0.000 claims description 85
- 229940127236 atypical antipsychotics Drugs 0.000 claims description 85
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 78
- 229960001534 risperidone Drugs 0.000 claims description 71
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 37
- 229960005017 olanzapine Drugs 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 30
- -1 QF-2400B Chemical compound 0.000 claims description 29
- QZUDBNBUXVUHMW-UHFFFAOYSA-N clozapine Chemical compound C1CN(C)CCN1C1=NC2=CC(Cl)=CC=C2NC2=CC=CC=C12 QZUDBNBUXVUHMW-UHFFFAOYSA-N 0.000 claims description 28
- 229960004170 clozapine Drugs 0.000 claims description 27
- 238000002560 therapeutic procedure Methods 0.000 claims description 24
- 239000002552 dosage form Substances 0.000 claims description 21
- DKMFBWQBDIGMHM-UHFFFAOYSA-N 1-(4-fluorophenyl)-4-(4-methyl-1-piperidinyl)-1-butanone Chemical compound C1CC(C)CCN1CCCC(=O)C1=CC=C(F)C=C1 DKMFBWQBDIGMHM-UHFFFAOYSA-N 0.000 claims description 19
- PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 claims description 19
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 claims description 19
- CYGODHVAJQTCBG-UHFFFAOYSA-N Bifeprunox Chemical compound C=12OC(=O)NC2=CC=CC=1N(CC1)CCN1CC(C=1)=CC=CC=1C1=CC=CC=C1 CYGODHVAJQTCBG-UHFFFAOYSA-N 0.000 claims description 19
- XVGOZDAJGBALKS-UHFFFAOYSA-N Blonanserin Chemical compound C1CN(CC)CCN1C1=CC(C=2C=CC(F)=CC=2)=C(CCCCCC2)C2=N1 XVGOZDAJGBALKS-UHFFFAOYSA-N 0.000 claims description 19
- JNNOSTQEZICQQP-UHFFFAOYSA-N N-desmethylclozapine Chemical compound N=1C2=CC(Cl)=CC=C2NC2=CC=CC=C2C=1N1CCNCC1 JNNOSTQEZICQQP-UHFFFAOYSA-N 0.000 claims description 19
- ZZQNEJILGNNOEP-UHFFFAOYSA-N Ocaperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC3=C(C)N=C4N(C3=O)C=CC=C4C)=NOC2=C1 ZZQNEJILGNNOEP-UHFFFAOYSA-N 0.000 claims description 19
- NTJOBXMMWNYJFB-UHFFFAOYSA-N amisulpride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(=O)(=O)CC)=C(N)C=C1OC NTJOBXMMWNYJFB-UHFFFAOYSA-N 0.000 claims description 19
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 claims description 19
- PQXKDMSYBGKCJA-CVTJIBDQSA-N lurasidone Chemical compound C1=CC=C2C(N3CCN(CC3)C[C@@H]3CCCC[C@H]3CN3C(=O)[C@@H]4[C@H]5CC[C@H](C5)[C@@H]4C3=O)=NSC2=C1 PQXKDMSYBGKCJA-CVTJIBDQSA-N 0.000 claims description 19
- GZKLJWGUPQBVJQ-UHFFFAOYSA-N sertindole Chemical compound C1=CC(F)=CC=C1N1C2=CC=C(Cl)C=C2C(C2CCN(CCN3C(NCC3)=O)CC2)=C1 GZKLJWGUPQBVJQ-UHFFFAOYSA-N 0.000 claims description 19
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 claims description 19
- HDOZVRUNCMBHFH-UHFFFAOYSA-N zotepine Chemical compound CN(C)CCOC1=CC2=CC=CC=C2SC2=CC=C(Cl)C=C12 HDOZVRUNCMBHFH-UHFFFAOYSA-N 0.000 claims description 19
- RTHCYVBBDHJXIQ-MRXNPFEDSA-N (R)-fluoxetine Chemical compound O([C@H](CCNC)C=1C=CC=CC=1)C1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-MRXNPFEDSA-N 0.000 claims description 18
- ICAXEUYZCLRXKY-UHFFFAOYSA-N 7-[3-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]propoxy]-3-(hydroxymethyl)chromen-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCCOC=3C=C4OC=C(C(C4=CC=3)=O)CO)=NOC2=C1 ICAXEUYZCLRXKY-UHFFFAOYSA-N 0.000 claims description 18
- 229950007013 abaperidone Drugs 0.000 claims description 18
- 229960003036 amisulpride Drugs 0.000 claims description 18
- 229960004372 aripiprazole Drugs 0.000 claims description 18
- 229960005245 asenapine Drugs 0.000 claims description 18
- 229950009087 bifeprunox Drugs 0.000 claims description 18
- 229950002871 blonanserin Drugs 0.000 claims description 18
- 229960002464 fluoxetine Drugs 0.000 claims description 18
- 229960003162 iloperidone Drugs 0.000 claims description 18
- LHAPOGAFBLSJJQ-GUTACTQSSA-N iti007 Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1.C([C@@H]1N2CCN(C=3C=CC=C(C2=3)[C@@H]1C1)C)CN1CCCC(=O)C1=CC=C(F)C=C1 LHAPOGAFBLSJJQ-GUTACTQSSA-N 0.000 claims description 18
- 229960001432 lurasidone Drugs 0.000 claims description 18
- 229960001861 melperone Drugs 0.000 claims description 18
- 229950010634 ocaperidone Drugs 0.000 claims description 18
- 229960001057 paliperidone Drugs 0.000 claims description 18
- 229950004193 perospirone Drugs 0.000 claims description 18
- GTAIPSDXDDTGBZ-OYRHEFFESA-N perospirone Chemical compound C1=CC=C2C(N3CCN(CC3)CCCCN3C(=O)[C@@H]4CCCC[C@@H]4C3=O)=NSCC2=C1 GTAIPSDXDDTGBZ-OYRHEFFESA-N 0.000 claims description 18
- 229960004431 quetiapine Drugs 0.000 claims description 18
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 18
- 229960000652 sertindole Drugs 0.000 claims description 18
- 229960000607 ziprasidone Drugs 0.000 claims description 18
- 229960004496 zotepine Drugs 0.000 claims description 18
- 208000009668 Neurobehavioral Manifestations Diseases 0.000 claims description 13
- 230000001225 therapeutic effect Effects 0.000 claims description 12
- 230000004044 response Effects 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 230000007370 cognitive improvement Effects 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- VSWBSWWIRNCQIJ-GJZGRUSLSA-N (R,R)-asenapine Chemical compound O1C2=CC=CC=C2[C@@H]2CN(C)C[C@H]2C2=CC(Cl)=CC=C21 VSWBSWWIRNCQIJ-GJZGRUSLSA-N 0.000 claims 5
- RTHCYVBBDHJXIQ-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]propan-1-amine Chemical compound C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 RTHCYVBBDHJXIQ-UHFFFAOYSA-N 0.000 claims 5
- 229940034173 symbyax Drugs 0.000 claims 5
- RDMFHRSPDKWERA-UHFFFAOYSA-N 5H-Pyrido[4,3-b]indole Chemical class C1=NC=C2C3=CC=CC=C3NC2=C1 RDMFHRSPDKWERA-UHFFFAOYSA-N 0.000 abstract description 45
- 150000003839 salts Chemical class 0.000 abstract description 42
- 150000001875 compounds Chemical class 0.000 description 162
- 239000003795 chemical substances by application Substances 0.000 description 70
- 230000000694 effects Effects 0.000 description 56
- 238000012360 testing method Methods 0.000 description 52
- 125000000217 alkyl group Chemical group 0.000 description 39
- 208000024891 symptom Diseases 0.000 description 38
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 37
- RGCVKNLCSQQDEP-UHFFFAOYSA-N Perphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 RGCVKNLCSQQDEP-UHFFFAOYSA-N 0.000 description 33
- 229960000762 perphenazine Drugs 0.000 description 33
- LNEPOXFFQSENCJ-UHFFFAOYSA-N haloperidol Chemical compound C1CC(O)(C=2C=CC(Cl)=CC=2)CCN1CCCC(=O)C1=CC=C(F)C=C1 LNEPOXFFQSENCJ-UHFFFAOYSA-N 0.000 description 29
- 230000015654 memory Effects 0.000 description 26
- 239000003814 drug Substances 0.000 description 25
- 125000004475 heteroaralkyl group Chemical group 0.000 description 24
- 125000003710 aryl alkyl group Chemical group 0.000 description 20
- 229940079593 drug Drugs 0.000 description 20
- 239000000164 antipsychotic agent Substances 0.000 description 16
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 16
- WFPIAZLQTJBIFN-DVZOWYKESA-N zuclopenthixol Chemical compound C1CN(CCO)CCN1CC\C=C\1C2=CC(Cl)=CC=C2SC2=CC=CC=C2/1 WFPIAZLQTJBIFN-DVZOWYKESA-N 0.000 description 16
- ZPEIMTDSQAKGNT-UHFFFAOYSA-N chlorpromazine Chemical compound C1=C(Cl)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 ZPEIMTDSQAKGNT-UHFFFAOYSA-N 0.000 description 15
- QLTXKCWMEZIHBJ-PJGJYSAQSA-N dizocilpine maleate Chemical compound OC(=O)\C=C/C(O)=O.C12=CC=CC=C2[C@]2(C)C3=CC=CC=C3C[C@H]1N2 QLTXKCWMEZIHBJ-PJGJYSAQSA-N 0.000 description 15
- 125000001072 heteroaryl group Chemical group 0.000 description 15
- 239000000902 placebo Substances 0.000 description 15
- 229940068196 placebo Drugs 0.000 description 15
- 229960004141 zuclopenthixol Drugs 0.000 description 15
- VSWBSWWIRNCQIJ-HUUCEWRRSA-N (S,S)-asenapine Chemical compound O1C2=CC=CC=C2[C@H]2CN(C)C[C@@H]2C2=CC(Cl)=CC=C21 VSWBSWWIRNCQIJ-HUUCEWRRSA-N 0.000 description 14
- PLDUPXSUYLZYBN-UHFFFAOYSA-N Fluphenazine Chemical compound C1CN(CCO)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 PLDUPXSUYLZYBN-UHFFFAOYSA-N 0.000 description 14
- KLPWJLBORRMFGK-UHFFFAOYSA-N Molindone Chemical compound O=C1C=2C(CC)=C(C)NC=2CCC1CN1CCOCC1 KLPWJLBORRMFGK-UHFFFAOYSA-N 0.000 description 14
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 14
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 14
- KLBQZWRITKRQQV-UHFFFAOYSA-N Thioridazine Chemical compound C12=CC(SC)=CC=C2SC2=CC=CC=C2N1CCC1CCCCN1C KLBQZWRITKRQQV-UHFFFAOYSA-N 0.000 description 14
- GFBKORZTTCHDGY-UWVJOHFNSA-N Thiothixene Chemical compound C12=CC(S(=O)(=O)N(C)C)=CC=C2SC2=CC=CC=C2\C1=C\CCN1CCN(C)CC1 GFBKORZTTCHDGY-UWVJOHFNSA-N 0.000 description 14
- 229960001076 chlorpromazine Drugs 0.000 description 14
- 229960003878 haloperidol Drugs 0.000 description 14
- YVUQSNJEYSNKRX-UHFFFAOYSA-N pimozide Chemical compound C1=CC(F)=CC=C1C(C=1C=CC(F)=CC=1)CCCN1CCC(N2C(NC3=CC=CC=C32)=O)CC1 YVUQSNJEYSNKRX-UHFFFAOYSA-N 0.000 description 14
- 208000028017 Psychotic disease Diseases 0.000 description 13
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 13
- 229960002690 fluphenazine Drugs 0.000 description 13
- 229960001374 fluphenazine decanoate Drugs 0.000 description 13
- VIQCGTZFEYDQMR-UHFFFAOYSA-N fluphenazine decanoate Chemical compound C1CN(CCOC(=O)CCCCCCCCC)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 VIQCGTZFEYDQMR-UHFFFAOYSA-N 0.000 description 13
- 229910052739 hydrogen Inorganic materials 0.000 description 13
- 239000001257 hydrogen Substances 0.000 description 13
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 13
- 229960000423 loxapine Drugs 0.000 description 13
- XJGVXQDUIWGIRW-UHFFFAOYSA-N loxapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2OC2=CC=C(Cl)C=C12 XJGVXQDUIWGIRW-UHFFFAOYSA-N 0.000 description 13
- 229960004938 molindone Drugs 0.000 description 13
- 229960003634 pimozide Drugs 0.000 description 13
- 229960003111 prochlorperazine Drugs 0.000 description 13
- WIKYUJGCLQQFNW-UHFFFAOYSA-N prochlorperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(Cl)=CC=C2SC2=CC=CC=C21 WIKYUJGCLQQFNW-UHFFFAOYSA-N 0.000 description 13
- 229960002784 thioridazine Drugs 0.000 description 13
- 229960005013 tiotixene Drugs 0.000 description 13
- 229960002324 trifluoperazine Drugs 0.000 description 13
- ZEWQUBUPAILYHI-UHFFFAOYSA-N trifluoperazine Chemical compound C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 ZEWQUBUPAILYHI-UHFFFAOYSA-N 0.000 description 13
- BXDAOUXDMHXPDI-UHFFFAOYSA-N trifluoperazine hydrochloride Chemical compound [H+].[H+].[Cl-].[Cl-].C1CN(C)CCN1CCCN1C2=CC(C(F)(F)F)=CC=C2SC2=CC=CC=C21 BXDAOUXDMHXPDI-UHFFFAOYSA-N 0.000 description 13
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 12
- 230000000903 blocking effect Effects 0.000 description 12
- 230000006870 function Effects 0.000 description 12
- 230000003291 dopaminomimetic effect Effects 0.000 description 11
- 108020003175 receptors Proteins 0.000 description 11
- 230000003442 weekly effect Effects 0.000 description 11
- 230000003935 attention Effects 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 230000006872 improvement Effects 0.000 description 10
- 102000005962 receptors Human genes 0.000 description 10
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 10
- 241000700159 Rattus Species 0.000 description 9
- 125000003118 aryl group Chemical group 0.000 description 9
- 230000008901 benefit Effects 0.000 description 9
- 210000004556 brain Anatomy 0.000 description 9
- 230000000848 glutamatergic effect Effects 0.000 description 9
- 125000005843 halogen group Chemical group 0.000 description 9
- 210000002569 neuron Anatomy 0.000 description 9
- 229950010883 phencyclidine Drugs 0.000 description 9
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 8
- 125000001246 bromo group Chemical group Br* 0.000 description 8
- 230000007423 decrease Effects 0.000 description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 8
- JTJMJGYZQZDUJJ-UHFFFAOYSA-N phencyclidine Chemical compound C1CCCCN1C1(C=2C=CC=CC=2)CCCCC1 JTJMJGYZQZDUJJ-UHFFFAOYSA-N 0.000 description 8
- 238000009097 single-agent therapy Methods 0.000 description 8
- 125000001424 substituent group Chemical group 0.000 description 8
- CYJQCYXRNNCURD-UHFFFAOYSA-N 2,8-dimethyl-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2C1CCN(C)C2 CYJQCYXRNNCURD-UHFFFAOYSA-N 0.000 description 7
- 101150049660 DRD2 gene Proteins 0.000 description 7
- 229940005529 antipsychotics Drugs 0.000 description 7
- 230000001149 cognitive effect Effects 0.000 description 7
- 230000000875 corresponding effect Effects 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 229960003638 dopamine Drugs 0.000 description 7
- 229930195712 glutamate Natural products 0.000 description 7
- 229940049906 glutamate Drugs 0.000 description 7
- 210000001320 hippocampus Anatomy 0.000 description 7
- 230000000698 schizophrenic effect Effects 0.000 description 7
- 229910052717 sulfur Chemical group 0.000 description 7
- 239000012730 sustained-release form Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 230000008859 change Effects 0.000 description 6
- 230000006735 deficit Effects 0.000 description 6
- 201000010099 disease Diseases 0.000 description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
- 230000009467 reduction Effects 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- VOROEQBFPPIACJ-SCSAIBSYSA-N (2r)-2-amino-5-phosphonopentanoic acid Chemical compound OC(=O)[C@H](N)CCCP(O)(O)=O VOROEQBFPPIACJ-SCSAIBSYSA-N 0.000 description 5
- 108050004812 Dopamine receptor Proteins 0.000 description 5
- 102000015554 Dopamine receptor Human genes 0.000 description 5
- 208000004547 Hallucinations Diseases 0.000 description 5
- 239000000654 additive Substances 0.000 description 5
- 230000000996 additive effect Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 210000003169 central nervous system Anatomy 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 229940076279 serotonin Drugs 0.000 description 5
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 4
- 108010072564 5-HT2A Serotonin Receptor Proteins 0.000 description 4
- 206010012239 Delusion Diseases 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical compound C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- 208000027089 Parkinsonian disease Diseases 0.000 description 4
- 206010034010 Parkinsonism Diseases 0.000 description 4
- 208000001431 Psychomotor Agitation Diseases 0.000 description 4
- 208000036752 Schizophrenia, paranoid type Diseases 0.000 description 4
- 206010043118 Tardive Dyskinesia Diseases 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 230000006399 behavior Effects 0.000 description 4
- 230000003542 behavioural effect Effects 0.000 description 4
- 210000004027 cell Anatomy 0.000 description 4
- 230000019771 cognition Effects 0.000 description 4
- 231100000868 delusion Toxicity 0.000 description 4
- 230000002068 genetic effect Effects 0.000 description 4
- 239000012729 immediate-release (IR) formulation Substances 0.000 description 4
- 230000007246 mechanism Effects 0.000 description 4
- 239000002609 medium Substances 0.000 description 4
- 230000001722 neurochemical effect Effects 0.000 description 4
- 230000008506 pathogenesis Effects 0.000 description 4
- 239000008194 pharmaceutical composition Substances 0.000 description 4
- 208000020016 psychiatric disease Diseases 0.000 description 4
- 230000002295 serotoninergic effect Effects 0.000 description 4
- 238000013268 sustained release Methods 0.000 description 4
- 230000001755 vocal effect Effects 0.000 description 4
- GTWLIQOLGOZTLF-UHFFFAOYSA-N 2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole;dihydrochloride Chemical compound Cl.Cl.C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CCC1=CC=C(C)N=C1 GTWLIQOLGOZTLF-UHFFFAOYSA-N 0.000 description 3
- 206010001540 Akathisia Diseases 0.000 description 3
- 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 3
- 208000020186 Schizophreniform disease Diseases 0.000 description 3
- 230000009471 action Effects 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- 238000004458 analytical method Methods 0.000 description 3
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 239000000969 carrier Substances 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 230000001684 chronic effect Effects 0.000 description 3
- 230000007012 clinical effect Effects 0.000 description 3
- 230000003247 decreasing effect Effects 0.000 description 3
- 239000008103 glucose Substances 0.000 description 3
- 230000001965 increasing effect Effects 0.000 description 3
- 230000003993 interaction Effects 0.000 description 3
- 230000033001 locomotion Effects 0.000 description 3
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 3
- 239000003176 neuroleptic agent Substances 0.000 description 3
- 230000000701 neuroleptic effect Effects 0.000 description 3
- 230000003285 pharmacodynamic effect Effects 0.000 description 3
- 229950000688 phenothiazine Drugs 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 230000002385 psychotomimetic effect Effects 0.000 description 3
- 125000004076 pyridyl group Chemical group 0.000 description 3
- 230000002441 reversible effect Effects 0.000 description 3
- 208000022610 schizoaffective disease Diseases 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 208000011580 syndromic disease Diseases 0.000 description 3
- 230000002195 synergetic effect Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 230000003936 working memory Effects 0.000 description 3
- CYJQCYXRNNCURD-DGCLKSJQSA-N (4ar,9bs)-2,8-dimethyl-1,3,4,4a,5,9b-hexahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2[C@@H]2[C@H]1CCN(C)C2 CYJQCYXRNNCURD-DGCLKSJQSA-N 0.000 description 2
- JIHMATXQZDSUOR-UHFFFAOYSA-N 2,3,4,4a,5,5a-hexahydro-1h-pyrido[4,3-b]indole Chemical class N1C2C=CC=CC2=C2C1CCNC2 JIHMATXQZDSUOR-UHFFFAOYSA-N 0.000 description 2
- BPPMRCNUQCVVFJ-UHFFFAOYSA-N 2,3,4,4a,5,9b-hexahydro-1h-pyrido[4,3-b]indole Chemical class N1C2=CC=CC=C2C2C1CCNC2 BPPMRCNUQCVVFJ-UHFFFAOYSA-N 0.000 description 2
- MUZFLDUALLSEBH-UHFFFAOYSA-N 2,8-dimethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(C)C=C2C2=C1CCN(C)C2 MUZFLDUALLSEBH-UHFFFAOYSA-N 0.000 description 2
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 2
- ASSKVPFEZFQQNQ-UHFFFAOYSA-N 2-benzoxazolinone Chemical compound C1=CC=C2OC(O)=NC2=C1 ASSKVPFEZFQQNQ-UHFFFAOYSA-N 0.000 description 2
- TWZCZLLZJDKWFN-UHFFFAOYSA-N 2-benzyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound C1CC=2NC3=CC=CC=C3C=2CN1CC1=CC=CC=C1 TWZCZLLZJDKWFN-UHFFFAOYSA-N 0.000 description 2
- MYUAGMGKBGUWEN-UHFFFAOYSA-N 2-ethyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCN(CC)C2 MYUAGMGKBGUWEN-UHFFFAOYSA-N 0.000 description 2
- VAOUGEMSRCFWTB-UHFFFAOYSA-N 2-methyl-5-[2-(2-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CCC1=CC=CN=C1C VAOUGEMSRCFWTB-UHFFFAOYSA-N 0.000 description 2
- NGNVOGPUTBVHTL-UHFFFAOYSA-N 5-benzyl-2,8-dimethyl-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(C)=CC=C1N2CC1=CC=CC=C1 NGNVOGPUTBVHTL-UHFFFAOYSA-N 0.000 description 2
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 2
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 2
- HFILMDDJKHXWEL-UHFFFAOYSA-N 8-bromo-2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=C(Br)C=C2C2=C1CCN(C)C2 HFILMDDJKHXWEL-UHFFFAOYSA-N 0.000 description 2
- WCTGYFWVYBPRGF-UHFFFAOYSA-N 8-chloro-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole Chemical compound C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CCC1=CC=C(C)N=C1 WCTGYFWVYBPRGF-UHFFFAOYSA-N 0.000 description 2
- 101000768857 Arabidopsis thaliana 3-phosphoshikimate 1-carboxyvinyltransferase, chloroplastic Proteins 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 208000012661 Dyskinesia Diseases 0.000 description 2
- 208000014094 Dystonic disease Diseases 0.000 description 2
- 208000027776 Extrapyramidal disease Diseases 0.000 description 2
- 239000007995 HEPES buffer Substances 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- YQEZLKZALYSWHR-UHFFFAOYSA-N Ketamine Chemical compound C=1C=CC=C(Cl)C=1C1(NC)CCCCC1=O YQEZLKZALYSWHR-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- CJUOSBUQOWKEKJ-UHFFFAOYSA-N Mebhydrolin napadisilate Chemical compound C1=CC=C2C(S(=O)(=O)O)=CC=CC2=C1S(O)(=O)=O.C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1.C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 CJUOSBUQOWKEKJ-UHFFFAOYSA-N 0.000 description 2
- 208000027626 Neurocognitive disease Diseases 0.000 description 2
- 241000288906 Primates Species 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000004480 active ingredient Substances 0.000 description 2
- 239000000556 agonist Substances 0.000 description 2
- 230000003281 allosteric effect Effects 0.000 description 2
- 238000010171 animal model Methods 0.000 description 2
- 239000005557 antagonist Substances 0.000 description 2
- 230000003288 anthiarrhythmic effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000000090 biomarker Substances 0.000 description 2
- 210000001772 blood platelet Anatomy 0.000 description 2
- 244000309464 bull Species 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 230000001713 cholinergic effect Effects 0.000 description 2
- 208000010877 cognitive disease Diseases 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 229950010754 dicarbine Drugs 0.000 description 2
- 108010093406 dopamine D1A receptor Proteins 0.000 description 2
- 239000003210 dopamine receptor blocking agent Substances 0.000 description 2
- 229950000904 dorastine Drugs 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 208000010118 dystonia Diseases 0.000 description 2
- 230000008030 elimination Effects 0.000 description 2
- 238000003379 elimination reaction Methods 0.000 description 2
- 230000008451 emotion Effects 0.000 description 2
- 239000000839 emulsion Substances 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 230000001667 episodic effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000007717 exclusion Effects 0.000 description 2
- 230000010326 executive functioning Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002349 favourable effect Effects 0.000 description 2
- 239000000835 fiber Substances 0.000 description 2
- 125000002541 furyl group Chemical group 0.000 description 2
- RZXHTPCHKSYGIB-UHFFFAOYSA-N gevotroline Chemical compound C1C=2C3=CC(F)=CC=C3NC=2CCN1CCCC1=CC=CN=C1 RZXHTPCHKSYGIB-UHFFFAOYSA-N 0.000 description 2
- 229950003589 gevotroline Drugs 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 230000036541 health Effects 0.000 description 2
- 150000002391 heterocyclic compounds Chemical class 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- PZOUSPYUWWUPPK-UHFFFAOYSA-N indole Natural products CC1=CC=CC2=C1C=CN2 PZOUSPYUWWUPPK-UHFFFAOYSA-N 0.000 description 2
- RKJUIXBNRJVNHR-UHFFFAOYSA-N indolenine Natural products C1=CC=C2CC=NC2=C1 RKJUIXBNRJVNHR-UHFFFAOYSA-N 0.000 description 2
- 238000007918 intramuscular administration Methods 0.000 description 2
- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 2
- 150000002500 ions Chemical class 0.000 description 2
- 230000002427 irreversible effect Effects 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 229960003299 ketamine Drugs 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000003340 mental effect Effects 0.000 description 2
- 230000036651 mood Effects 0.000 description 2
- 230000000877 morphologic effect Effects 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 230000001537 neural effect Effects 0.000 description 2
- 230000001067 neuroprotector Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 238000009520 phase I clinical trial Methods 0.000 description 2
- 238000009521 phase II clinical trial Methods 0.000 description 2
- 210000002442 prefrontal cortex Anatomy 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 230000000506 psychotropic effect Effects 0.000 description 2
- 230000003252 repetitive effect Effects 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
- 230000000392 somatic effect Effects 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 238000010561 standard procedure Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 description 1
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- MGRVRXRGTBOSHW-UHFFFAOYSA-N (aminomethyl)phosphonic acid Chemical compound NCP(O)(O)=O MGRVRXRGTBOSHW-UHFFFAOYSA-N 0.000 description 1
- 150000008591 2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indoles Chemical class 0.000 description 1
- RPROHCOBMVQVIV-UHFFFAOYSA-N 2,3,4,5-tetrahydro-1h-pyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCNC2 RPROHCOBMVQVIV-UHFFFAOYSA-N 0.000 description 1
- ZVVRLIBBDZISSN-UHFFFAOYSA-N 2-[2-(4-benzo[b][1,4]benzothiazepin-1-ylpiperazin-1-yl)ethoxy]ethanol Chemical compound C1CN(CCOCCO)CCN1C1=CC=CC2=C1SC1=CC=CC=C1C=N2 ZVVRLIBBDZISSN-UHFFFAOYSA-N 0.000 description 1
- KISWVXRQTGLFGD-UHFFFAOYSA-N 2-[[2-[[6-amino-2-[[2-[[2-[[5-amino-2-[[2-[[1-[2-[[6-amino-2-[(2,5-diamino-5-oxopentanoyl)amino]hexanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxypropanoyl]amino]-5-oxopentanoyl]amino]-5-(diaminomethylideneamino)p Chemical compound C1CCN(C(=O)C(CCCN=C(N)N)NC(=O)C(CCCCN)NC(=O)C(N)CCC(N)=O)C1C(=O)NC(CO)C(=O)NC(CCC(N)=O)C(=O)NC(CCCN=C(N)N)C(=O)NC(CO)C(=O)NC(CCCCN)C(=O)NC(C(=O)NC(CC(C)C)C(O)=O)CC1=CC=C(O)C=C1 KISWVXRQTGLFGD-UHFFFAOYSA-N 0.000 description 1
- SPBXLWNNWOLJEO-UHFFFAOYSA-N 2-[[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]methyl]-1,2,3,9-tetrahydrocarbazol-4-one Chemical compound N1C2=CC=CC=C2C(C(=O)C2)=C1CC2CN(CC1)CCC1C1=NOC2=CC(F)=CC=C21 SPBXLWNNWOLJEO-UHFFFAOYSA-N 0.000 description 1
- FYHWPFXPFFPQRT-UHFFFAOYSA-N 2-methyl-1,3,4,5-tetrahydropyrido[4,3-b]indole Chemical compound N1C2=CC=CC=C2C2=C1CCN(C)C2 FYHWPFXPFFPQRT-UHFFFAOYSA-N 0.000 description 1
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 description 1
- XMIIGOLPHOKFCH-UHFFFAOYSA-N 3-phenylpropionic acid Chemical compound OC(=O)CCC1=CC=CC=C1 XMIIGOLPHOKFCH-UHFFFAOYSA-N 0.000 description 1
- ZVMSBRKYDZGHQV-UHFFFAOYSA-N 3a,4,5,6,7,7a-hexahydroisoindole-1,3-dione;hydrochloride Chemical compound Cl.C1CCCC2C(=O)NC(=O)C21 ZVMSBRKYDZGHQV-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- PPRXPSDHSSUMRZ-UHFFFAOYSA-N 5-benzyl-2-methyl-3,4-dihydro-1h-pyrido[4,3-b]indole;dihydrochloride Chemical compound Cl.Cl.C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 PPRXPSDHSSUMRZ-UHFFFAOYSA-N 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
- XGGILFZLGXIRFW-UHFFFAOYSA-N 8-chloro-2-methyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1h-pyrido[4,3-b]indole;dihydrochloride Chemical compound Cl.Cl.C1N(C)CCC2=C1C1=CC(Cl)=CC=C1N2CCC1=CC=C(C)N=C1 XGGILFZLGXIRFW-UHFFFAOYSA-N 0.000 description 1
- MDALANRXHSLQQX-UHFFFAOYSA-N 8-fluoro-2-(3-pyridin-3-ylpropyl)-1,3,4,5-tetrahydropyrido[4,3-b]indole;dihydrochloride Chemical compound Cl.Cl.C1C=2C3=CC(F)=CC=C3NC=2CCN1CCCC1=CC=CN=C1 MDALANRXHSLQQX-UHFFFAOYSA-N 0.000 description 1
- RYYNUNOYGCZRSB-UHFFFAOYSA-N 9-chloro-1-(4-methylpiperazin-1-yl)-11H-benzo[b][1,4]benzodiazepine Chemical compound C1CN(C)CCN1C1=CC=CC2=C1NC1=CC(Cl)=CC=C1C=N2 RYYNUNOYGCZRSB-UHFFFAOYSA-N 0.000 description 1
- 206010001022 Acute psychosis Diseases 0.000 description 1
- 206010001488 Aggression Diseases 0.000 description 1
- 208000024827 Alzheimer disease Diseases 0.000 description 1
- 206010003805 Autism Diseases 0.000 description 1
- 208000020706 Autistic disease Diseases 0.000 description 1
- 206010006100 Bradykinesia Diseases 0.000 description 1
- 108010074051 C-Reactive Protein Proteins 0.000 description 1
- 102100032752 C-reactive protein Human genes 0.000 description 1
- 241000282693 Cercopithecidae Species 0.000 description 1
- 208000017667 Chronic Disease Diseases 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 102000000634 Cytochrome c oxidase subunit IV Human genes 0.000 description 1
- 108090000365 Cytochrome-c oxidases Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 208000035859 Drug effect increased Diseases 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
- 108090000790 Enzymes Proteins 0.000 description 1
- 206010060891 General symptom Diseases 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- 102000018899 Glutamate Receptors Human genes 0.000 description 1
- 108010027915 Glutamate Receptors Proteins 0.000 description 1
- 206010061991 Grimacing Diseases 0.000 description 1
- 206010019070 Hallucination, auditory Diseases 0.000 description 1
- 101000959820 Homo sapiens Interferon alpha-1/13 Proteins 0.000 description 1
- 208000023105 Huntington disease Diseases 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 208000006083 Hypokinesia Diseases 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- 108010002350 Interleukin-2 Proteins 0.000 description 1
- 208000015592 Involuntary movements Diseases 0.000 description 1
- 102000004310 Ion Channels Human genes 0.000 description 1
- 108090000862 Ion Channels Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- 208000032443 Masked facies Diseases 0.000 description 1
- 208000001145 Metabolic Syndrome Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 208000016285 Movement disease Diseases 0.000 description 1
- 102000047918 Myelin Basic Human genes 0.000 description 1
- 101710107068 Myelin basic protein Proteins 0.000 description 1
- 229940099433 NMDA receptor antagonist Drugs 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000007072 Nerve Growth Factors Human genes 0.000 description 1
- 201000005625 Neuroleptic malignant syndrome Diseases 0.000 description 1
- 208000011644 Neurologic Gait disease Diseases 0.000 description 1
- 102000016387 Pancreatic elastase Human genes 0.000 description 1
- 108010067372 Pancreatic elastase Proteins 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 206010071390 Resting tremor Diseases 0.000 description 1
- 206010038743 Restlessness Diseases 0.000 description 1
- 206010039897 Sedation Diseases 0.000 description 1
- 208000028810 Shared psychotic disease Diseases 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 241000248418 Tetrahymena pyriformis Species 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 108060008682 Tumor Necrosis Factor Proteins 0.000 description 1
- ZVQOOHYFBIDMTQ-UHFFFAOYSA-N [methyl(oxido){1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-lambda(6)-sulfanylidene]cyanamide Chemical compound N#CN=S(C)(=O)C(C)C1=CC=C(C(F)(F)F)N=C1 ZVQOOHYFBIDMTQ-UHFFFAOYSA-N 0.000 description 1
- 201000000690 abdominal obesity-metabolic syndrome Diseases 0.000 description 1
- 208000028752 abnormal posture Diseases 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 208000012761 aggressive behavior Diseases 0.000 description 1
- 230000016571 aggressive behavior Effects 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 description 1
- 230000002539 anti-aggressive effect Effects 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000003416 antiarrhythmic agent Substances 0.000 description 1
- 229940124623 antihistamine drug Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940082988 antihypertensives serotonin antagonists Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003420 antiserotonin agent Substances 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000035045 associative learning Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 210000004227 basal ganglia Anatomy 0.000 description 1
- 208000013404 behavioral symptom Diseases 0.000 description 1
- 238000013542 behavioral therapy Methods 0.000 description 1
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 244000309466 calf Species 0.000 description 1
- 239000007894 caplet Substances 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000007681 cardiovascular toxicity Effects 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 206010007776 catatonia Diseases 0.000 description 1
- 238000000423 cell based assay Methods 0.000 description 1
- 238000002659 cell therapy Methods 0.000 description 1
- 210000001638 cerebellum Anatomy 0.000 description 1
- 210000003710 cerebral cortex Anatomy 0.000 description 1
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 239000011248 coating agent Substances 0.000 description 1
- 230000007278 cognition impairment Effects 0.000 description 1
- 230000003930 cognitive ability Effects 0.000 description 1
- 229940126214 compound 3 Drugs 0.000 description 1
- 230000003750 conditioning effect Effects 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 230000009260 cross reactivity Effects 0.000 description 1
- 125000006165 cyclic alkyl group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 230000001934 delay Effects 0.000 description 1
- 238000012217 deletion Methods 0.000 description 1
- 230000037430 deletion Effects 0.000 description 1
- 230000003001 depressive effect Effects 0.000 description 1
- 230000006866 deterioration Effects 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 1
- 229940005501 dopaminergic agent Drugs 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000004064 dysfunction Effects 0.000 description 1
- 238000003372 electrophysiological method Methods 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- DEFVIWRASFVYLL-UHFFFAOYSA-N ethylene glycol bis(2-aminoethyl)tetraacetic acid Chemical compound OC(=O)CN(CC(O)=O)CCOCCOCCN(CC(O)=O)CC(O)=O DEFVIWRASFVYLL-UHFFFAOYSA-N 0.000 description 1
- 230000004438 eyesight Effects 0.000 description 1
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical group C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 229940125384 geroprotector Drugs 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002989 glutamic acid Drugs 0.000 description 1
- ZDXPYRJPNDTMRX-UHFFFAOYSA-N glutamine Natural products OC(=O)C(N)CCC(N)=O ZDXPYRJPNDTMRX-UHFFFAOYSA-N 0.000 description 1
- 102000005396 glutamine synthetase Human genes 0.000 description 1
- 108020002326 glutamine synthetase Proteins 0.000 description 1
- 230000000285 glutaminergic effect Effects 0.000 description 1
- 230000012010 growth Effects 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 125000001475 halogen functional group Chemical group 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 125000005842 heteroatom Chemical group 0.000 description 1
- 210000004295 hippocampal neuron Anatomy 0.000 description 1
- 230000003284 homeostatic effect Effects 0.000 description 1
- QRMZSPFSDQBLIX-UHFFFAOYSA-N homovanillic acid Chemical compound COC1=CC(CC(O)=O)=CC=C1O QRMZSPFSDQBLIX-UHFFFAOYSA-N 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 230000036543 hypotension Effects 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000000099 in vitro assay Methods 0.000 description 1
- 150000002475 indoles Chemical class 0.000 description 1
- 125000003406 indolizinyl group Chemical group C=1(C=CN2C=CC=CC12)* 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 230000003834 intracellular effect Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000006194 liquid suspension Substances 0.000 description 1
- 230000004807 localization Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- FQQIIPAOSKSOJM-UHFFFAOYSA-N mebhydrolin Chemical compound C1N(C)CCC2=C1C1=CC=CC=C1N2CC1=CC=CC=C1 FQQIIPAOSKSOJM-UHFFFAOYSA-N 0.000 description 1
- 229960004934 mebhydrolin Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- 230000003924 mental process Effects 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 210000001616 monocyte Anatomy 0.000 description 1
- 230000037023 motor activity Effects 0.000 description 1
- 230000004118 muscle contraction Effects 0.000 description 1
- 230000017311 musculoskeletal movement, spinal reflex action Effects 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000007922 nasal spray Substances 0.000 description 1
- 229940097496 nasal spray Drugs 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000010082 neurochemical mechanism Effects 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 208000015122 neurodegenerative disease Diseases 0.000 description 1
- 230000000926 neurological effect Effects 0.000 description 1
- 230000002887 neurotoxic effect Effects 0.000 description 1
- 239000003900 neurotrophic factor Substances 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 229940100688 oral solution Drugs 0.000 description 1
- 239000007935 oral tablet Substances 0.000 description 1
- 229940096978 oral tablet Drugs 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 238000006213 oxygenation reaction Methods 0.000 description 1
- 238000004806 packaging method and process Methods 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 150000002978 peroxides Chemical class 0.000 description 1
- 230000002688 persistence Effects 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 125000004194 piperazin-1-yl group Chemical group [H]N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 description 1
- 229920000729 poly(L-lysine) polymer Polymers 0.000 description 1
- 238000002600 positron emission tomography Methods 0.000 description 1
- 238000011886 postmortem examination Methods 0.000 description 1
- 230000001144 postural effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000002360 prefrontal effect Effects 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000006513 pyridinyl methyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 229940106887 risperdal Drugs 0.000 description 1
- 238000011300 routine therapy Methods 0.000 description 1
- 230000036280 sedation Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 239000007905 soft elastic gelatin capsule Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000011593 sulfur Chemical group 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000004083 survival effect Effects 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 230000024587 synaptic transmission, glutamatergic Effects 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229940126585 therapeutic drug Drugs 0.000 description 1
- 230000004797 therapeutic response Effects 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 230000002446 thrombocytic effect Effects 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 238000011269 treatment regimen Methods 0.000 description 1
- 102000003390 tumor necrosis factor Human genes 0.000 description 1
- 230000007497 verbal memory Effects 0.000 description 1
- 230000016776 visual perception Effects 0.000 description 1
- 230000010389 voluntary attention Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
- 230000004584 weight gain Effects 0.000 description 1
- 235000019786 weight gain Nutrition 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 230000036642 wellbeing Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- 239000012224 working solution Substances 0.000 description 1
Classifications
-
- 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
- A61K31/33—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
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- 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
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Epidemiology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| RU2007129567 | 2007-08-01 | ||
| RU2007129567/15A RU2508106C2 (ru) | 2007-08-01 | 2007-08-01 | Способы и композиции для лечения шизофрении с использованием атипичной нейролептической комбинированной терапии |
| RU2007129568 | 2007-08-01 | ||
| RU2007129568/15A RU2508096C2 (ru) | 2007-08-01 | 2007-08-01 | Способы и композиции для лечения шизофрении с использованием нейролептической комбинированной терапии |
| PCT/US2008/009357 WO2009017836A1 (en) | 2007-08-01 | 2008-08-01 | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2719824A1 true CA2719824A1 (en) | 2009-02-05 |
Family
ID=40304696
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2719824A Abandoned CA2719824A1 (en) | 2007-08-01 | 2008-08-01 | Methods and compositions for treating schizophrenia using antipsychotic combination therapy |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US20110269777A1 (https=) |
| EP (1) | EP2175724A4 (https=) |
| JP (1) | JP2010535220A (https=) |
| KR (1) | KR20100054812A (https=) |
| CN (1) | CN101842010A (https=) |
| AU (1) | AU2008282742A1 (https=) |
| BR (1) | BRPI0815850A2 (https=) |
| CA (1) | CA2719824A1 (https=) |
| MX (1) | MX2010001218A (https=) |
| WO (1) | WO2009017836A1 (https=) |
Families Citing this family (74)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US7837812B2 (en) | 2004-05-21 | 2010-11-23 | Ati Properties, Inc. | Metastable beta-titanium alloys and methods of processing the same by direct aging |
| AU2008302751A1 (en) | 2007-09-20 | 2009-03-26 | D2E, Llc | Fluoro-containing derivatives of hydrogenated pyrido[4,3-b]indoles with neuroprotective and cognition enhancing properties, process for preparing, and use |
| RU2007139634A (ru) | 2007-10-25 | 2009-04-27 | Сергей Олегович Бачурин (RU) | Новые тиазол-, триазол- или оксадиазол-содержащие тетрациклические соединения |
| RU2544856C2 (ru) * | 2008-01-25 | 2015-03-20 | Сергей Олегович Бачурин | НОВЫЕ ПРОИЗВОДНЫЕ 2,3,4,5-ТЕТРАГИДРО-1-ПИРИДО[4,3-b]ИНДОЛА И СПОСОБЫ ИХ ПРИМЕНЕНИЯ |
| CN102046625B (zh) | 2008-03-24 | 2015-04-08 | 梅迪维新技术公司 | 桥连杂环化合物及其使用方法 |
| TWI443098B (zh) | 2008-03-24 | 2014-07-01 | Medivation Technologies Inc | 吡啶并〔３，４－ｂ〕吲哚及使用方法 |
| CN105168219B (zh) | 2008-05-27 | 2018-11-20 | 细胞内治疗公司 | 用于睡眠障碍和其他疾病的方法和组合物 |
| AU2009308706C1 (en) | 2008-10-31 | 2016-01-21 | Medivation Technologies, Inc. | Pyrido (4,3-b) indoles containing rigid moieties |
| WO2010051503A1 (en) | 2008-10-31 | 2010-05-06 | Medivation Technologies, Inc. | Azepino [4, 5-b] indoles and methods of use |
| KR20110132564A (ko) | 2009-02-11 | 2011-12-08 | 선오비온 파마슈티컬스 인코포레이티드 | 히스타민 ｈ3 역 작용제 및 길항제, 및 이의 사용 방법 |
| EP2581374B1 (en) * | 2009-04-10 | 2014-03-19 | Institute of Pharmacology and Toxicology Academy of Military Medical Sciences P.L.A. China | Preparation of tetrahydropyrido[4,3-b]indole derivatives |
| CA2760541A1 (en) * | 2009-04-29 | 2010-11-04 | Medivation Technologies, Inc. | Pyrido[4,3-b] indoles and methods of use |
| JP5827943B2 (ja) | 2009-04-29 | 2015-12-02 | メディベイション テクノロジーズ， インコーポレイテッド | ピリド［４，３−ｂ］インドールおよびその使用方法 |
| WO2011038163A1 (en) | 2009-09-23 | 2011-03-31 | Medivation Technologies, Inc. | Pyrido[3,4-b]indoles and methods of use |
| AU2010298169B2 (en) | 2009-09-23 | 2015-10-29 | Medivation Technologies, Inc. | Bridged heterocyclic compounds and methods of use |
| EP2480078A4 (en) | 2009-09-23 | 2013-03-06 | Medivation Technologies Inc | PYRIDO- [4,3-B] INDOLE AND USE METHOD THEREFOR |
| WO2011103485A1 (en) * | 2010-02-18 | 2011-08-25 | Medivation Technologies, Inc. | Fused tetracyclic pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US9193728B2 (en) | 2010-02-18 | 2015-11-24 | Medivation Technologies, Inc. | Fused tetracyclic pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| US9034865B2 (en) | 2010-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido [4,3-B] indole and pyrido [3,4-B] indole derivatives and methods of use |
| WO2011103448A1 (en) * | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Methods and compositions for treating psychotic disorders using antipsychotic combination therapy |
| WO2011103430A1 (en) | 2010-02-19 | 2011-08-25 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| JP6138491B2 (ja) | 2010-02-24 | 2017-05-31 | ザ ブロード インスティテュート， インコーポレイテッド | 感染性疾患の病原体およびそれらの薬剤感受性を診断する方法 |
| CN103476417A (zh) | 2011-02-18 | 2013-12-25 | 梅迪维新技术公司 | 治疗糖尿病的化合物和方法 |
| US9035056B2 (en) | 2011-02-18 | 2015-05-19 | Medivation Technologies, Inc. | Pyrido[4,3-b]indole and pyrido[3,4-b]indole derivatives and methods of use |
| US20140155384A1 (en) | 2011-02-18 | 2014-06-05 | Medivation Technologies, Inc. | Compounds and methods of treating diabetes |
| US9434747B2 (en) | 2011-02-18 | 2016-09-06 | Medivation Technologies, Inc. | Methods of treating diabetes |
| WO2013040419A1 (en) * | 2011-09-14 | 2013-03-21 | The Trustees Of Columbia University In The City Of New York | Compositions and methods for treating hyperprolinemia-associated mental disorders |
| US10039813B2 (en) | 2012-02-07 | 2018-08-07 | Massachusetts Institute Of Technology | Use of antagonists of ghrelin or ghrelin receptor to prevent or treat stress-sensitive psychiatric illness |
| WO2013155504A1 (en) | 2012-04-14 | 2013-10-17 | Intra-Cellular Therapies, Inc. | Novel methods |
| WO2014128882A1 (ja) * | 2013-02-21 | 2014-08-28 | 医療法人 和楽会 | 不安うつ病の治療薬 |
| WO2014144231A1 (en) | 2013-03-15 | 2014-09-18 | Massachusetts Institute Of Technology | Use of antagonists of growth hormone or growth hormone receptor to prevent or treat stress-sensitive psychiatric illness |
| HUE053159T2 (hu) | 2013-03-15 | 2021-06-28 | Intra Cellular Therapies Inc | Szerves vegyületek |
| IL305990B2 (en) | 2013-12-03 | 2025-12-01 | Intra Cellular Therapies Inc | Long-acting injectable composition comprising polymeric microspheres of heterocycle fused gamma-carboline compounds or a pharmaceutical composition for sustained or delayed release comprising the compounds and their use in the treatment of bipolar disorder i and/or bipolar ii disorder |
| MX365969B (es) | 2014-04-04 | 2019-06-21 | Intra Cellular Therapies Inc | Gamma-carbolinas fusionadas con heterociclos sustituidas con deuterio. |
| KR101646962B1 (ko) | 2014-09-29 | 2016-08-10 | 한국과학기술연구원 | CaM 저해활성을 가지는 페노싸이아진 유도체 |
| US20160184290A1 (en) * | 2014-12-31 | 2016-06-30 | Paul J. Markovitz | Method of treating schizophrenia |
| WO2016138099A1 (en) | 2015-02-24 | 2016-09-01 | Massachusetts Institute Of Technology | Use of ghrelin or functional ghrelin receptor agonists to prevent and treat stress-sensitive psychiatric illness |
| WO2016205631A1 (en) * | 2015-06-17 | 2016-12-22 | Massachusetts Institute Of Technology | Serotonin 2c receptor antagonists to prevent and treat stress-related trauma disorders |
| CN108883111B (zh) | 2016-01-26 | 2021-10-08 | 细胞内治疗公司 | 有机化合物 |
| PL3407889T3 (pl) | 2016-03-25 | 2021-11-22 | Intra-Cellular Therapies, Inc. | Związki organiczne i ich zastosowanie w leczeniu lub zapobieganiu zaburzeniom ośrodkowego układu nerwowego |
| JP2019513143A (ja) | 2016-03-28 | 2019-05-23 | イントラ−セルラー・セラピーズ・インコーポレイテッドＩｎｔｒａ−Ｃｅｌｌｕｌａｒ Ｔｈｅｒａｐｉｅｓ， Ｉｎｃ． | 新規塩類および結晶 |
| US11014925B2 (en) | 2016-03-28 | 2021-05-25 | Intra-Cellular Therapies, Inc. | Co-crystals of 1-(4-fluoro-phenyl)-4-((6bR,1OaS)-3-methyl-2,3,6b,9,10,10a-hexahydro-1H,7H- pyrido[3′,4′:4,51_pyrrolo [1,2,3-delqcuinoxalin-8-yl)-butan-1-one with nicotinamide or isonicotinamide |
| EP3436083A4 (en) | 2016-03-28 | 2019-11-27 | Intra-Cellular Therapies, Inc. | NOVEL COMPOSITIONS AND METHOD |
| US11331316B2 (en) | 2016-10-12 | 2022-05-17 | Intra-Cellular Therapies, Inc. | Amorphous solid dispersions |
| ES2769286T3 (es) | 2016-12-20 | 2020-06-25 | Lts Lohmann Therapie Systeme Ag | Sistema terapéutico transdérmico que contiene asenapina |
| WO2018115010A1 (en) | 2016-12-20 | 2018-06-28 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine and polysiloxane or polyisobutylene |
| US10906906B2 (en) | 2016-12-29 | 2021-02-02 | Intra-Cellular Therapies, Inc. | Organic compounds |
| US10961245B2 (en) | 2016-12-29 | 2021-03-30 | Intra-Cellular Therapies, Inc. | Substituted heterocycle fused gamma-carbolines for treatment of central nervous system disorders |
| KR102793584B1 (ko) | 2016-12-31 | 2025-04-09 | 바이오엑셀 테라퓨틱스 인코포레이티드 | 불안의 치료를 위한 설하 덱스메데토미딘의 용도 |
| IL268970B2 (en) | 2017-03-24 | 2023-12-01 | Intra Cellular Therapies Inc | Oral transmucosal formulations of substituted heterocycle fused gamma carbolines |
| US10035795B1 (en) | 2017-04-06 | 2018-07-31 | Korea Institute Of Science And Technology | Phenothiazine derivatives having CaM inhibitory activity |
| ES2881783T3 (es) | 2017-06-26 | 2021-11-30 | Lts Lohmann Therapie Systeme Ag | Sistema terapéutico transdérmico que contiene asenapina y polímero de acrílico y silicona |
| JP7223742B2 (ja) | 2017-07-26 | 2023-02-16 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| JP7224333B2 (ja) | 2017-07-26 | 2023-02-17 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 有機化合物 |
| CN111107847A (zh) | 2017-09-26 | 2020-05-05 | 细胞内治疗公司 | 新的盐和晶体 |
| WO2019128991A1 (en) * | 2017-12-26 | 2019-07-04 | Sunshine Lake Pharma Co., Ltd. | Lurasidone solid dispersion and preparation method thereof |
| WO2019178484A1 (en) | 2018-03-16 | 2019-09-19 | Intra-Cellular Therapies, Inc. | Novel methods |
| AU2019240226B2 (en) | 2018-03-23 | 2024-11-28 | Intra-Cellular Therapies, Inc. | Organic compounds |
| IL321985A (en) | 2018-06-06 | 2025-09-01 | Intra Cellular Therapies Inc | New salts and crystals |
| WO2019237037A1 (en) | 2018-06-08 | 2019-12-12 | Intra-Cellular Therapies, Inc. | Novel methods |
| CN112533593A (zh) | 2018-06-20 | 2021-03-19 | 罗曼治疗系统股份公司 | 含有阿塞那平的透皮治疗系统 |
| CA3101420A1 (en) | 2018-06-20 | 2019-12-26 | Lts Lohmann Therapie-Systeme Ag | Transdermal therapeutic system containing asenapine |
| PL3813802T3 (pl) | 2018-06-27 | 2025-04-22 | Bioxcel Therapeutics, Inc. | Formulacje błony zawierające deksmedetomidynę i sposoby ich wytwarzania |
| EP3843729A4 (en) | 2018-08-29 | 2022-06-01 | Intra-Cellular Therapies, Inc. | NOVEL COMPOSITIONS AND PROCESSES |
| CN112584837A (zh) | 2018-08-31 | 2021-03-30 | 细胞内治疗公司 | 新方法 |
| CA3108558A1 (en) | 2018-08-31 | 2020-03-05 | Intra-Cellular Therapies, Inc. | Novel methods |
| US12195463B2 (en) | 2018-12-21 | 2025-01-14 | Intra-Cellular Therapies, Inc. | Organic compounds |
| JP7673040B2 (ja) | 2019-07-07 | 2025-05-08 | イントラ－セルラー・セラピーズ・インコーポレイテッド | 新規方法 |
| EP3999058A4 (en) | 2019-07-19 | 2023-05-03 | Bioxcel Therapeutics, Inc. | NON-SEDATIVE DEXMEDETOMIDINE-BASED TREATMENT REGIMEN |
| EP4072554A4 (en) | 2019-12-11 | 2023-12-20 | Intra-Cellular Therapies, Inc. | ORGANIC CONNECTION |
| TW202302094A (zh) * | 2021-02-26 | 2023-01-16 | 美商百歐克斯賽爾治療公司 | 用於治療激躁之方法及組合物 |
| US12414948B2 (en) | 2022-05-18 | 2025-09-16 | Intra-Cellular Therapies, Inc. | Methods |
| CN115290775A (zh) * | 2022-07-25 | 2022-11-04 | 上海市徐汇区中心医院 | 一种精神类药物质控品、其试剂盒、制备方法及应用 |
| US11806334B1 (en) | 2023-01-12 | 2023-11-07 | Bioxcel Therapeutics, Inc. | Non-sedating dexmedetomidine treatment regimens |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CS229067B1 (en) * | 1981-08-20 | 1984-04-16 | Svorad Stolc | Medicinal preparation with antiarhythmic and supporting effect applied with hypoxia,and method of preparing active substance thereof |
| US4672117A (en) * | 1985-09-16 | 1987-06-09 | American Home Products Corporation | Antipsychotic gamma-carbolines |
| US5300645A (en) * | 1993-04-14 | 1994-04-05 | Eli Lilly And Company | Tetrahydro-pyrido-indole |
| US5631265A (en) * | 1994-03-11 | 1997-05-20 | Eli Lilly And Company | 8-substituted tetrahydro-beta-carbolines |
| RU2140417C1 (ru) * | 1995-10-17 | 1999-10-27 | Институт физиологически активных веществ РАН | Производные гидрированных пиридо(4,3-b)индолов, способы их получения, фармацевтическая композиция и способ лечения |
| TW470745B (en) * | 1996-05-23 | 2002-01-01 | Janssen Pharmaceutica Nv | Hexahydro-pyrido[4,3-b]indole derivatives |
| US6849640B2 (en) * | 2001-08-08 | 2005-02-01 | Pharmacia & Upjohn Company | Therapeutic 1H-pyrido [4,3-b] indoles |
| WO2005120463A1 (en) * | 2004-06-09 | 2005-12-22 | Ranbaxy Laboratories Limited | Rapidly disintegrating tablets of risperidone |
| WO2007041697A2 (en) * | 2005-10-04 | 2007-04-12 | Medivation, Inc. | Hydrogenated pyrido-indole compounds for the treatment of huntington ' s disease |
| US20070112017A1 (en) * | 2005-10-31 | 2007-05-17 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
| RU2338537C2 (ru) * | 2006-01-25 | 2008-11-20 | Сергей Олегович Бачурин | СРЕДСТВО ДЛЯ ЛЕЧЕНИЯ ШИЗОФРЕНИИ НА ОСНОВЕ ГИДРИРОВАННЫХ ПИРИДО(4,3-b)ИНДОЛОВ (ВАРИАНТЫ), ФАРМАКОЛОГИЧЕСКОЕ СРЕДСТВО НА ЕГО ОСНОВЕ И СПОСОБ ЕГО ПРИМЕНЕНИЯ |
| JP2010528016A (ja) * | 2007-05-25 | 2010-08-19 | メディベーション ニューロロジー， インコーポレイテッド | 細胞を刺激するための方法および組成物 |
-
2008
- 2008-08-01 WO PCT/US2008/009357 patent/WO2009017836A1/en not_active Ceased
- 2008-08-01 CA CA2719824A patent/CA2719824A1/en not_active Abandoned
- 2008-08-01 BR BRPI0815850-9A2A patent/BRPI0815850A2/pt not_active IP Right Cessation
- 2008-08-01 US US12/671,679 patent/US20110269777A1/en not_active Abandoned
- 2008-08-01 EP EP08826868A patent/EP2175724A4/en not_active Withdrawn
- 2008-08-01 JP JP2010519954A patent/JP2010535220A/ja active Pending
- 2008-08-01 AU AU2008282742A patent/AU2008282742A1/en not_active Abandoned
- 2008-08-01 MX MX2010001218A patent/MX2010001218A/es not_active Application Discontinuation
- 2008-08-01 CN CN200880107277A patent/CN101842010A/zh active Pending
- 2008-08-01 KR KR1020107004429A patent/KR20100054812A/ko not_active Withdrawn
Also Published As
| Publication number | Publication date |
|---|---|
| EP2175724A4 (en) | 2010-09-15 |
| WO2009017836A1 (en) | 2009-02-05 |
| KR20100054812A (ko) | 2010-05-25 |
| MX2010001218A (es) | 2010-04-07 |
| US20110269777A1 (en) | 2011-11-03 |
| CN101842010A (zh) | 2010-09-22 |
| EP2175724A1 (en) | 2010-04-21 |
| AU2008282742A1 (en) | 2009-02-05 |
| BRPI0815850A2 (pt) | 2014-10-07 |
| JP2010535220A (ja) | 2010-11-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US20110269777A1 (en) | Methods and compositions for treating schizophrenia using antipsychotic combination therapy | |
| US20070225316A1 (en) | Methods and compositions for treating schizophrenia | |
| US12528819B2 (en) | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment | |
| US20230107032A1 (en) | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment | |
| JP2024072291A (ja) | 同種抗体により駆動される慢性移植片対宿主病を処置及び予防する方法 | |
| CN115996716A (zh) | Eif4a抑制剂组合 | |
| US20150352107A1 (en) | Alpha7 neuronal nicotinic receptor ligand and antipsychotic compositions | |
| WO2005063296A2 (en) | Therapeutic combination for cognition enhancement and psychotic disorders | |
| JP2010507672A (ja) | アルツハイマー病を治療するための方法および組み合わせ治療 | |
| TW200538128A (en) | Therapeutic combinations of atypical antipsychotics with corticotropin releasing factor antagonists | |
| CA3123897A1 (en) | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment | |
| KR20160065776A (ko) | 재발성 악성 신경교종 또는 진행성 2차 뇌종양의 치료를 위한 디안히드로갈락티톨 및 그의 유사체 및 유도체의 용도 | |
| DK2608670T3 (en) | METHOD OF TREATING ANTI-SOCIETY-INDICATED WEIGHT RISE | |
| MX2010009390A (es) | Kit, composicion, producto o medicamento para tratar deterioro cognitivo. | |
| RU2508106C2 (ru) | Способы и композиции для лечения шизофрении с использованием атипичной нейролептической комбинированной терапии | |
| US11505555B2 (en) | Benzodiazepine derivatives, compositions, and methods for treating cognitive impairment | |
| RU2508096C2 (ru) | Способы и композиции для лечения шизофрении с использованием нейролептической комбинированной терапии | |
| WO2025229051A1 (en) | Use of atr inhibitors in combination with antiandrogen agent | |
| EP2296471A1 (en) | Muscarinic agonists as cognitive enhancers | |
| HK1224581A1 (en) | Use of dianhydrogalactitol and analogs and derivatives thereof to treat recurrent malignant glioma or progressive secondary brian tumor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FZDE | Discontinued |
Effective date: 20140801 |