NZ198657A - Anxiolytic compositions containing a benzodiazepine and a phenanthridine analgesic - Google Patents
Anxiolytic compositions containing a benzodiazepine and a phenanthridine analgesicInfo
- Publication number
- NZ198657A NZ198657A NZ198657A NZ19865781A NZ198657A NZ 198657 A NZ198657 A NZ 198657A NZ 198657 A NZ198657 A NZ 198657A NZ 19865781 A NZ19865781 A NZ 19865781A NZ 198657 A NZ198657 A NZ 198657A
- Authority
- NZ
- New Zealand
- Prior art keywords
- benzodiazepine
- hydrogen
- chloro
- phenyl
- formula
- Prior art date
Links
- 229940049706 benzodiazepine Drugs 0.000 title claims description 71
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title claims description 50
- 239000000203 mixture Substances 0.000 title claims description 29
- RDOWQLZANAYVLL-UHFFFAOYSA-N phenanthridine Chemical compound C1=CC=C2C3=CC=CC=C3C=NC2=C1 RDOWQLZANAYVLL-UHFFFAOYSA-N 0.000 title description 14
- 230000000949 anxiolytic effect Effects 0.000 title description 5
- 239000002249 anxiolytic agent Substances 0.000 title description 4
- 230000000202 analgesic effect Effects 0.000 title description 2
- 230000027455 binding Effects 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 50
- 239000001257 hydrogen Substances 0.000 claims description 50
- 229960003529 diazepam Drugs 0.000 claims description 37
- FFVXQGMUHIJQAO-BFKQJKLPSA-N levonantradol Chemical compound C([C@@H](C)OC=1C=C(OC(C)=O)C=2[C@@H]3C[C@H](O)CC[C@H]3[C@H](C)NC=2C=1)CCC1=CC=CC=C1 FFVXQGMUHIJQAO-BFKQJKLPSA-N 0.000 claims description 32
- 229950005812 levonantradol Drugs 0.000 claims description 32
- 239000000730 antalgic agent Substances 0.000 claims description 28
- 241000699670 Mus sp. Species 0.000 claims description 22
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 150000001875 compounds Chemical class 0.000 claims description 22
- 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 claims description 20
- 150000002431 hydrogen Chemical class 0.000 claims description 19
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 19
- 102000004300 GABA-A Receptors Human genes 0.000 claims description 17
- 108090000839 GABA-A Receptors Proteins 0.000 claims description 17
- 238000000034 method Methods 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 15
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 150000003839 salts Chemical class 0.000 claims description 13
- CWRVKFFCRWGWCS-UHFFFAOYSA-N Pentrazole Chemical compound C1CCCCC2=NN=NN21 CWRVKFFCRWGWCS-UHFFFAOYSA-N 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- GUJAGMICFDYKNR-UHFFFAOYSA-N 1,4-benzodiazepine Chemical compound N1C=CN=CC2=CC=CC=C12 GUJAGMICFDYKNR-UHFFFAOYSA-N 0.000 claims description 8
- 125000001589 carboacyl group Chemical group 0.000 claims description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 239000002253 acid Substances 0.000 claims description 6
- 125000004423 acyloxy group Chemical group 0.000 claims description 5
- 230000001773 anti-convulsant effect Effects 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- CDCHDCWJMGXXRH-UHFFFAOYSA-N estazolam Chemical compound C=1C(Cl)=CC=C(N2C=NN=C2CN=2)C=1C=2C1=CC=CC=C1 CDCHDCWJMGXXRH-UHFFFAOYSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 230000008569 process Effects 0.000 claims description 5
- 125000004076 pyridyl group Chemical group 0.000 claims description 5
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 4
- 239000001961 anticonvulsive agent Substances 0.000 claims description 4
- 229960003965 antiepileptics Drugs 0.000 claims description 4
- 238000002474 experimental method Methods 0.000 claims description 4
- 125000001153 fluoro group Chemical group F* 0.000 claims description 4
- 206010053398 Clonic convulsion Diseases 0.000 claims description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
- 229950000251 nantradol Drugs 0.000 description 17
- 210000004556 brain Anatomy 0.000 description 15
- 229960002200 flunitrazepam Drugs 0.000 description 15
- 239000012528 membrane Substances 0.000 description 15
- FFVXQGMUHIJQAO-KXUCESEGSA-N [(6s,6ar,9r,10ar)-9-hydroxy-6-methyl-3-(5-phenylpentan-2-yloxy)-5,6,6a,7,8,9,10,10a-octahydrophenanthridin-1-yl] acetate Chemical compound C=1([C@@H]2C[C@H](O)CC[C@H]2[C@H](C)NC=1C=1)C(OC(C)=O)=CC=1OC(C)CCCC1=CC=CC=C1 FFVXQGMUHIJQAO-KXUCESEGSA-N 0.000 description 12
- 241000699666 Mus <mouse, genus> Species 0.000 description 11
- 241000700159 Rattus Species 0.000 description 11
- 150000001557 benzodiazepines Chemical class 0.000 description 11
- 239000000872 buffer Substances 0.000 description 10
- 238000001727 in vivo Methods 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000001054 cortical effect Effects 0.000 description 8
- -1 lactone disaccharide Chemical class 0.000 description 7
- 239000007983 Tris buffer Substances 0.000 description 6
- 238000000338 in vitro Methods 0.000 description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 6
- 230000002708 enhancing effect Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 230000009870 specific binding Effects 0.000 description 5
- 239000003981 vehicle Substances 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 229940079593 drug Drugs 0.000 description 4
- 239000003814 drug Substances 0.000 description 4
- 239000003446 ligand Substances 0.000 description 4
- 239000008188 pellet Substances 0.000 description 4
- 239000011780 sodium chloride Substances 0.000 description 4
- 238000011282 treatment Methods 0.000 description 4
- KWVPFECTOKLOBL-KTKRTIGZSA-N 2-[(z)-octadec-9-enoxy]ethanol Chemical compound CCCCCCCC\C=C/CCCCCCCCOCCO KWVPFECTOKLOBL-KTKRTIGZSA-N 0.000 description 3
- 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 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
- 241000124008 Mammalia Species 0.000 description 3
- PPTYJKAXVCCBDU-UHFFFAOYSA-N Rohypnol Chemical compound N=1CC(=O)N(C)C2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1F PPTYJKAXVCCBDU-UHFFFAOYSA-N 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000000144 pharmacologic effect Effects 0.000 description 3
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 238000009395 breeding Methods 0.000 description 2
- 230000001488 breeding effect Effects 0.000 description 2
- 210000003169 central nervous system Anatomy 0.000 description 2
- ANTSCNMPPGJYLG-UHFFFAOYSA-N chlordiazepoxide Chemical compound O=N=1CC(NC)=NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ANTSCNMPPGJYLG-UHFFFAOYSA-N 0.000 description 2
- 229960004782 chlordiazepoxide Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 2
- 239000003365 glass fiber Substances 0.000 description 2
- 238000011534 incubation Methods 0.000 description 2
- 238000010253 intravenous injection Methods 0.000 description 2
- 239000002207 metabolite Substances 0.000 description 2
- 238000003359 percent control normalization Methods 0.000 description 2
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 description 2
- 230000003389 potentiating effect Effects 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 238000002203 pretreatment Methods 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 238000007619 statistical method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 239000000725 suspension Substances 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 1
- QCIKUTXSFDIBHH-BCHNQVDYSA-N (2r,3r,4s,5r)-2-[6-[[2-(4-chlorophenyl)-3-bicyclo[2.2.2]octanyl]amino]purin-9-yl]-5-(hydroxymethyl)oxolane-3,4-diol Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C2=NC=NC(NC3C(C4CCC3CC4)C=3C=CC(Cl)=CC=3)=C2N=C1 QCIKUTXSFDIBHH-BCHNQVDYSA-N 0.000 description 1
- ACWUGIFUVOOAEX-UHFFFAOYSA-N (9-hydroxyphenanthridin-1-yl) acetate Chemical compound C(C)(=O)OC1=CC=CC2=NC=C3C=CC(=CC3=C12)O ACWUGIFUVOOAEX-UHFFFAOYSA-N 0.000 description 1
- QKNYBSVHEMOAJP-UHFFFAOYSA-N 2-amino-2-(hydroxymethyl)propane-1,3-diol;hydron;chloride Chemical compound Cl.OCC(N)(CO)CO QKNYBSVHEMOAJP-UHFFFAOYSA-N 0.000 description 1
- MSWZFWKMSRAUBD-IVMDWMLBSA-N 2-amino-2-deoxy-D-glucopyranose Chemical compound N[C@H]1C(O)O[C@H](CO)[C@@H](O)[C@@H]1O MSWZFWKMSRAUBD-IVMDWMLBSA-N 0.000 description 1
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 description 1
- SEADJJCWSPCSHY-UHFFFAOYSA-N 2h-2,4-benzodiazepine Chemical class N1C=NC=C2C=CC=CC2=C1 SEADJJCWSPCSHY-UHFFFAOYSA-N 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- 239000005660 Abamectin Substances 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 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
- 239000002126 C01EB10 - Adenosine Substances 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- AEMRFAOFKBGASW-UHFFFAOYSA-M Glycolate Chemical compound OCC([O-])=O AEMRFAOFKBGASW-UHFFFAOYSA-M 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 229910002651 NO3 Inorganic materials 0.000 description 1
- VEQPNABPJHWNSG-UHFFFAOYSA-N Nickel(2+) Chemical compound [Ni+2] VEQPNABPJHWNSG-UHFFFAOYSA-N 0.000 description 1
- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- TYTNJHKTKQNNKL-UHFFFAOYSA-N [9-hydroxy-5,6-dimethyl-3-(5-phenylpentan-2-yloxy)-6a,7,8,9,10,10a-hexahydro-6h-phenanthridin-1-yl] acetate Chemical compound C=1C(OC(C)=O)=C2C3CC(O)CCC3C(C)N(C)C2=CC=1OC(C)CCCC1=CC=CC=C1 TYTNJHKTKQNNKL-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229960005305 adenosine Drugs 0.000 description 1
- 230000008485 antagonism Effects 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 239000007900 aqueous suspension Substances 0.000 description 1
- RRZXIRBKKLTSOM-XPNPUAGNSA-N avermectin B1a Chemical compound C1=C[C@H](C)[C@@H]([C@@H](C)CC)O[C@]11O[C@H](C\C=C(C)\[C@@H](O[C@@H]2O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C2)[C@@H](C)\C=C\C=C/2[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\2)O)C[C@H]4C1 RRZXIRBKKLTSOM-XPNPUAGNSA-N 0.000 description 1
- 230000006399 behavior Effects 0.000 description 1
- MSWZFWKMSRAUBD-UHFFFAOYSA-N beta-D-galactosamine Natural products NC1C(O)OC(CO)C(O)C1O MSWZFWKMSRAUBD-UHFFFAOYSA-N 0.000 description 1
- 238000012925 biological evaluation Methods 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 229940001468 citrate Drugs 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000001186 cumulative effect Effects 0.000 description 1
- RHKZVMUBMXGOLL-UHFFFAOYSA-N cyclopentolate hydrochloride Chemical compound Cl.C1CCCC1(O)C(C(=O)OCCN(C)C)C1=CC=CC=C1 RHKZVMUBMXGOLL-UHFFFAOYSA-N 0.000 description 1
- 229940075144 cylate Drugs 0.000 description 1
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- 230000003028 elevating effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 229960002442 glucosamine Drugs 0.000 description 1
- 230000005484 gravity Effects 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 239000003701 inert diluent Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000010255 intramuscular injection Methods 0.000 description 1
- 239000007927 intramuscular injection Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 229940049920 malate Drugs 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N malic acid Chemical compound OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- ZJQHPWUVQPJPQT-UHFFFAOYSA-N muscimol Chemical compound NCC1=CC(=O)NO1 ZJQHPWUVQPJPQT-UHFFFAOYSA-N 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 229910001453 nickel ion Inorganic materials 0.000 description 1
- 230000009871 nonspecific binding Effects 0.000 description 1
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 1
- 125000001129 phenylbutoxy group Chemical group [*]OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- MOODSJOROWROTO-UHFFFAOYSA-N salicylsulfuric acid Chemical compound OC(=O)C1=CC=CC=C1OS(O)(=O)=O MOODSJOROWROTO-UHFFFAOYSA-N 0.000 description 1
- 238000003345 scintillation counting Methods 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 230000001624 sedative effect Effects 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 229940071103 sulfosalicylate Drugs 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Anesthesiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US06/197,872 US4320124A (en) | 1980-10-17 | 1980-10-17 | Composition for enhancing binding of a benzodiazepine to central benzodiazepine receptors and use thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NZ198657A true NZ198657A (en) | 1985-05-31 |
Family
ID=22731077
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NZ198657A NZ198657A (en) | 1980-10-17 | 1981-10-15 | Anxiolytic compositions containing a benzodiazepine and a phenanthridine analgesic |
Country Status (10)
| Country | Link |
|---|---|
| US (1) | US4320124A (ref) |
| EP (1) | EP0050487B1 (ref) |
| JP (1) | JPS5795912A (ref) |
| KR (1) | KR830007074A (ref) |
| AU (1) | AU529307B2 (ref) |
| DE (1) | DE3166349D1 (ref) |
| GR (1) | GR75097B (ref) |
| IL (1) | IL64062A0 (ref) |
| NZ (1) | NZ198657A (ref) |
| PT (1) | PT73746B (ref) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4406888A (en) * | 1981-01-09 | 1983-09-27 | Pfizer Inc. | Aqueous micellar solutions of levonantradol and N-methyllevonantradol and lyophilic forms thereof for reconstitution |
| US6031098A (en) * | 1997-08-11 | 2000-02-29 | California Institute Of Technology | Detection and treatment of duplex polynucleotide damage |
| US6617321B2 (en) * | 1997-09-30 | 2003-09-09 | Eli Lilly And Company | 2-methyl-thieno-benzodiazepine formulation |
| US20030199496A1 (en) * | 2002-04-22 | 2003-10-23 | Simon David Lew | Pharmaceutical compositions containing alpha3beta4 nicotinic receptor antagonists and methods of their use |
| US20090156565A1 (en) * | 2004-12-03 | 2009-06-18 | The Children's Hospital Of Philadelphia | Composition and use thereof in enhancing a therapeutic effect of an antiepileptic drug |
| US7932249B2 (en) * | 2005-01-05 | 2011-04-26 | Eli Lilly And Company | Olanzapine pamoate dihydrate |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3862986A (en) * | 1966-07-01 | 1975-01-28 | Hoffmann La Roche | 1-Hydroxymethyl-amino-2-alkyl-or allyl-2-(3{40 -methoxy-phenyl)-chclohexanes |
| ZA772899B (en) * | 1976-05-17 | 1978-04-26 | Pfizer | 9-hydroxyhexahydrobenzol(c)quinolines and intermediates therefor |
| US4206225A (en) * | 1978-09-22 | 1980-06-03 | Pfizer Inc. | 2,10-Disubstituted dibenzo[b,d]pyrans and benzo[c]quinolines |
| US4228169A (en) * | 1979-06-26 | 1980-10-14 | Pfizer Inc. | 1,9-Dihydroxyoctahydrobenzo[c]quinolines and 1-hydroxyhexahydrobenzo[c]quinoline-9(8H)-ones as antiemetic agents |
-
1980
- 1980-10-17 US US06/197,872 patent/US4320124A/en not_active Expired - Lifetime
-
1981
- 1981-09-30 PT PT73746A patent/PT73746B/pt unknown
- 1981-10-13 GR GR66267A patent/GR75097B/el unknown
- 1981-10-15 NZ NZ198657A patent/NZ198657A/en unknown
- 1981-10-16 JP JP56165567A patent/JPS5795912A/ja active Pending
- 1981-10-16 KR KR1019810003920A patent/KR830007074A/ko not_active Abandoned
- 1981-10-16 IL IL64062A patent/IL64062A0/xx unknown
- 1981-10-16 EP EP81304822A patent/EP0050487B1/en not_active Expired
- 1981-10-16 DE DE8181304822T patent/DE3166349D1/de not_active Expired
- 1981-10-16 AU AU76517/81A patent/AU529307B2/en not_active Ceased
Also Published As
| Publication number | Publication date |
|---|---|
| PT73746A (en) | 1981-10-01 |
| GR75097B (ref) | 1984-07-13 |
| JPS5795912A (en) | 1982-06-15 |
| KR830007074A (ko) | 1983-10-14 |
| PT73746B (en) | 1983-11-08 |
| EP0050487A1 (en) | 1982-04-28 |
| AU529307B2 (en) | 1983-06-02 |
| IL64062A0 (en) | 1982-01-31 |
| US4320124A (en) | 1982-03-16 |
| EP0050487B1 (en) | 1984-09-26 |
| AU7651781A (en) | 1982-04-22 |
| DE3166349D1 (en) | 1984-10-31 |
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