CZ200434A3 - Léčivo pro léčení abnormálního úzkosného chování u domácích zvířat a způsob screeningu zkoušené sloučeniny za účelem stanovení anxiolytické účinnosti u psů - Google Patents
Léčivo pro léčení abnormálního úzkosného chování u domácích zvířat a způsob screeningu zkoušené sloučeniny za účelem stanovení anxiolytické účinnosti u psů Download PDFInfo
- Publication number
- CZ200434A3 CZ200434A3 CZ200434A CZ200434A CZ200434A3 CZ 200434 A3 CZ200434 A3 CZ 200434A3 CZ 200434 A CZ200434 A CZ 200434A CZ 200434 A CZ200434 A CZ 200434A CZ 200434 A3 CZ200434 A3 CZ 200434A3
- Authority
- CZ
- Czechia
- Prior art keywords
- methoxybenzylamino
- phenylpiperidine
- azabicyclo
- diphenylmethyl
- cis
- Prior art date
Links
- 230000002159 abnormal effect Effects 0.000 title claims abstract description 39
- 241001465754 Metazoa Species 0.000 title claims abstract description 36
- 230000006400 anxiety behaviour Effects 0.000 title claims abstract description 24
- 241000282472 Canis lupus familiaris Species 0.000 title claims description 61
- 239000003814 drug Substances 0.000 title claims description 10
- 238000000034 method Methods 0.000 title abstract description 13
- 150000001875 compounds Chemical class 0.000 title description 56
- 230000000949 anxiolytic effect Effects 0.000 title description 11
- 238000012216 screening Methods 0.000 title description 6
- 102000002002 Neurokinin-1 Receptors Human genes 0.000 claims abstract description 39
- 108010040718 Neurokinin-1 Receptors Proteins 0.000 claims abstract description 39
- 239000002464 receptor antagonist Substances 0.000 claims abstract description 29
- 229940044551 receptor antagonist Drugs 0.000 claims abstract description 29
- 208000013403 hyperactivity Diseases 0.000 claims description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 10
- -1 (2-methoxynaphth-1-ylmethylamino) -2-phenylpiperidine Chemical compound 0.000 claims description 8
- 230000006378 damage Effects 0.000 claims description 7
- 230000028327 secretion Effects 0.000 claims description 5
- 125000000972 4,5-dimethylthiazol-2-yl group Chemical group [H]C([H])([H])C1=C(N=C(*)S1)C([H])([H])[H] 0.000 claims description 4
- 230000037406 food intake Effects 0.000 claims description 4
- 235000012631 food intake Nutrition 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- 230000007958 sleep Effects 0.000 claims description 4
- 206010016275 Fear Diseases 0.000 claims description 3
- 239000012530 fluid Substances 0.000 claims description 3
- 208000019899 phobic disease Diseases 0.000 claims description 3
- DTQNEFOKTXXQKV-HKUYNNGSSA-N (2s,3s)-n-[(2-methoxyphenyl)methyl]-2-phenylpiperidin-3-amine Chemical compound COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)NCCC1 DTQNEFOKTXXQKV-HKUYNNGSSA-N 0.000 claims description 2
- PRXRQNXEYXMJCK-NSIYGSDQSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2,5-dimethoxyphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(OC)C=1)OC)[H])C1=CC=CC=C1 PRXRQNXEYXMJCK-NSIYGSDQSA-N 0.000 claims description 2
- BXCXPWYLAUEXBY-IKFSTVPESA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2,5-dimethoxyphenyl)methylamino]-n,n-diethyl-1-azabicyclo[2.2.2]octane-5-carboxamide Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(=O)N(CC)CC)([C@@H]1NCC=1C(=CC=C(OC)C=1)OC)[H])C1=CC=CC=C1 BXCXPWYLAUEXBY-IKFSTVPESA-N 0.000 claims description 2
- GKJVNRHHOMPGSG-NSIYGSDQSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2-methoxy-5-methylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C)C=1)OC)[H])C1=CC=CC=C1 GKJVNRHHOMPGSG-NSIYGSDQSA-N 0.000 claims description 2
- ZBFJTKASKIUJNF-PHXFNYRRSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2-methoxy-5-methylsulfinylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C=1)S(C)=O)OC)[H])C1=CC=CC=C1 ZBFJTKASKIUJNF-PHXFNYRRSA-N 0.000 claims description 2
- NNQJDQUAJJRYRV-NSIYGSDQSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2-methoxy-5-methylsulfonylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C=1)S(C)(=O)=O)OC)[H])C1=CC=CC=C1 NNQJDQUAJJRYRV-NSIYGSDQSA-N 0.000 claims description 2
- UGYNIDYASJFWTR-FXZOGHEHSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2-methoxy-5-propan-2-ylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C=1)C(C)C)OC)[H])C1=CC=CC=C1 UGYNIDYASJFWTR-FXZOGHEHSA-N 0.000 claims description 2
- UCSKUOLGIXJPLU-FXZOGHEHSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(2-methoxy-5-propylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(CCC)C=1)OC)[H])C1=CC=CC=C1 UCSKUOLGIXJPLU-FXZOGHEHSA-N 0.000 claims description 2
- FQMDWRVWAZOFJF-QUNNAWRHSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(5-butan-2-yl-2-methoxyphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C=1)C(C)CC)OC)[H])C1=CC=CC=C1 FQMDWRVWAZOFJF-QUNNAWRHSA-N 0.000 claims description 2
- NOTNLZQKHMFVKX-MTDVLGRSSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(6-methoxy-6-methylsulfanylcyclohexa-2,4-dien-1-yl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC1C(C=CC=C1)(OC)SC)[H])C1=CC=CC=C1 NOTNLZQKHMFVKX-MTDVLGRSSA-N 0.000 claims description 2
- LVCKDBYHCLGPDR-LSGCGUROSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[[2-methoxy-5-(trifluoromethoxy)phenyl]methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical class C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(OC(F)(F)F)C=1)OC)[H])C1=CC=CC=C1 LVCKDBYHCLGPDR-LSGCGUROSA-N 0.000 claims description 2
- LBYSHULELVFOGE-ATACATFBSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[[5-(dimethylamino)-2-methoxyphenyl]methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(C=1)N(C)C)OC)[H])C1=CC=CC=C1 LBYSHULELVFOGE-ATACATFBSA-N 0.000 claims description 2
- BNUOLJBGGUPSKO-YVYLOCOQSA-N (2s,3s,4s,5r)-2-benzhydryl-n,n-diethyl-3-[(2-methoxy-5-propan-2-ylphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxamide Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(=O)N(CC)CC)([C@@H]1NCC=1C(=CC=C(C=1)C(C)C)OC)[H])C1=CC=CC=C1 BNUOLJBGGUPSKO-YVYLOCOQSA-N 0.000 claims description 2
- DKWJWICVVLNEFV-UHFFFAOYSA-N 2-benzhydryl-n-[2-methoxy-5-(trifluoromethoxy)phenyl]-2-methyl-1-azabicyclo[2.2.2]octan-3-amine Chemical compound COC1=CC=C(OC(F)(F)F)C=C1NC1C(C(C=2C=CC=CC=2)C=2C=CC=CC=2)(C)N2CCC1CC2 DKWJWICVVLNEFV-UHFFFAOYSA-N 0.000 claims description 2
- 125000006499 2-trifluoromethoxy benzyl group Chemical group [H]C1=C([H])C(OC(F)(F)F)=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 2
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 2
- HIORMPAWFMQDOW-ZCYQVOJMSA-N 6-[(2s,3s)-3-[(2-methoxyphenyl)methylamino]-2-phenylpiperidin-1-yl]hexan-1-ol Chemical compound COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)N(CCCCCCO)CCC1 HIORMPAWFMQDOW-ZCYQVOJMSA-N 0.000 claims description 2
- ZGACJMVLEGDHNP-CWAVIJBDSA-N CC(C)CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(C)C.CC(N=C(C)S1)=C1S(O)(=O)=O Chemical compound CC(C)CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(C)C.CC(N=C(C)S1)=C1S(O)(=O)=O ZGACJMVLEGDHNP-CWAVIJBDSA-N 0.000 claims description 2
- OXVZEEKXZNKIKY-IUQUCOCYSA-N CC(C)CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC.CC(N=C(C)S1)=C1S(O)(=O)=O Chemical compound CC(C)CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC.CC(N=C(C)S1)=C1S(O)(=O)=O OXVZEEKXZNKIKY-IUQUCOCYSA-N 0.000 claims description 2
- VRSXHEWKYHOMTM-DTRWSJPISA-N CC(C)NC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC.CC(N=C(C)S1)=C1S(O)(=O)=O Chemical compound CC(C)NC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC.CC(N=C(C)S1)=C1S(O)(=O)=O VRSXHEWKYHOMTM-DTRWSJPISA-N 0.000 claims description 2
- UPKMFZMGQHTZTP-MKSBGGEFSA-N CC(N=C(C)S1)=C1S(O)(=O)=O.CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC Chemical compound CC(N=C(C)S1)=C1S(O)(=O)=O.CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC UPKMFZMGQHTZTP-MKSBGGEFSA-N 0.000 claims description 2
- AXNWANHXOICNMX-QQTWVUFVSA-N CC1=C(C)SC(S(O)(=O)=O)=N1.CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(F)(F)F Chemical compound CC1=C(C)SC(S(O)(=O)=O)=N1.CNC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(F)(F)F AXNWANHXOICNMX-QQTWVUFVSA-N 0.000 claims description 2
- 241000283086 Equidae Species 0.000 claims description 2
- 241000282326 Felis catus Species 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 2
- KXCUGLQCBUEEQE-AHWVRZQESA-N n,2,4-trimethyl-n-[3-[[[(2s,3s)-2-phenylpiperidin-3-yl]amino]methyl]-4-propan-2-yloxyphenyl]-1,3-thiazole-5-sulfonamide Chemical compound C1([C@@H]2NCCC[C@@H]2NCC2=CC(=CC=C2OC(C)C)N(C)S(=O)(=O)C2=C(N=C(C)S2)C)=CC=CC=C1 KXCUGLQCBUEEQE-AHWVRZQESA-N 0.000 claims description 2
- XXXAPFHGQOEKLI-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-2,4-diphenylpiperidin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NCCC1C1=CC=CC=C1 XXXAPFHGQOEKLI-UHFFFAOYSA-N 0.000 claims description 2
- SZFRAFLMDAIGLU-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-4-methyl-2-phenylpiperidin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NCCC1C SZFRAFLMDAIGLU-UHFFFAOYSA-N 0.000 claims description 2
- MYORKKSQSYUQSH-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-5-methyl-2-phenylpiperidin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NCC(C)C1 MYORKKSQSYUQSH-UHFFFAOYSA-N 0.000 claims description 2
- DBKJGIXLYZJDMI-UHFFFAOYSA-N n-[(2-methoxyphenyl)methyl]-6-methyl-2-phenylpiperidin-3-amine Chemical compound COC1=CC=CC=C1CNC1C(C=2C=CC=CC=2)NC(C)CC1 DBKJGIXLYZJDMI-UHFFFAOYSA-N 0.000 claims description 2
- UQCMZYGKYBKFKH-GMAHTHKFSA-N n-[4-methoxy-3-[[[(2s,3s)-2-phenylpiperidin-3-yl]amino]methyl]phenyl]-4,5-dimethyl-1,3-thiazol-2-amine Chemical compound C1=C(CN[C@@H]2[C@@H](NCCC2)C=2C=CC=CC=2)C(OC)=CC=C1NC1=NC(C)=C(C)S1 UQCMZYGKYBKFKH-GMAHTHKFSA-N 0.000 claims description 2
- LWMPFIOTEAXAGV-UHFFFAOYSA-N piperidin-1-amine Chemical compound NN1CCCCC1 LWMPFIOTEAXAGV-UHFFFAOYSA-N 0.000 claims description 2
- QFTQKCRAJOXJNK-DKJKITOUSA-N (2s,3s)-2-benzhydryl-n-(5-butan-2-yl-2-methoxyphenyl)-2-methyl-1-azabicyclo[2.2.2]octan-3-amine Chemical compound CCC(C)C1=CC=C(OC)C(N[C@@H]2[C@](N3CCC2CC3)(C)C(C=2C=CC=CC=2)C=2C=CC=CC=2)=C1 QFTQKCRAJOXJNK-DKJKITOUSA-N 0.000 claims 1
- HDGOKGLEAJIUED-LAUBAEHRSA-N (2s,3s)-3-[[5-tert-butyl-2-(trifluoromethoxy)phenyl]methyl]-2-phenylpiperidin-1-amine Chemical compound CC(C)(C)C1=CC=C(OC(F)(F)F)C(C[C@H]2[C@H](N(N)CCC2)C=2C=CC=CC=2)=C1 HDGOKGLEAJIUED-LAUBAEHRSA-N 0.000 claims 1
- HANWCAQDYMDUKN-ATACATFBSA-N (2s,3s,4s,5r)-2-benzhydryl-3-[(5-ethyl-2-methoxyphenyl)methylamino]-1-azabicyclo[2.2.2]octane-5-carboxylic acid Chemical compound C=1C=CC=CC=1C([C@@H]1N2CC[C@@]([C@H](C2)C(O)=O)([C@@H]1NCC=1C(=CC=C(CC)C=1)OC)[H])C1=CC=CC=C1 HANWCAQDYMDUKN-ATACATFBSA-N 0.000 claims 1
- ZGBXROBHDHIQGY-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-sulfonic acid Chemical compound CC1=NC(C)=C(S(O)(=O)=O)S1 ZGBXROBHDHIQGY-UHFFFAOYSA-N 0.000 claims 1
- LAOMAAZAXGILTO-WNJJXGMVSA-N 4-[(2s,3s)-3-[(2-methoxyphenyl)methylamino]-2-phenylpiperidin-1-yl]-1-phenylbutan-1-one Chemical compound COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)N(CCCC(=O)C=2C=CC=CC=2)CCC1 LAOMAAZAXGILTO-WNJJXGMVSA-N 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- XUWVIABDWDTJRZ-UHFFFAOYSA-N propan-2-ylazanide Chemical compound CC(C)[NH-] XUWVIABDWDTJRZ-UHFFFAOYSA-N 0.000 claims 1
- 238000012360 testing method Methods 0.000 description 35
- 238000011282 treatment Methods 0.000 description 33
- 239000000902 placebo Substances 0.000 description 26
- 229940068196 placebo Drugs 0.000 description 26
- 208000019901 Anxiety disease Diseases 0.000 description 25
- 238000000926 separation method Methods 0.000 description 25
- 230000006399 behavior Effects 0.000 description 22
- 239000002609 medium Substances 0.000 description 17
- 230000000638 stimulation Effects 0.000 description 15
- 230000036506 anxiety Effects 0.000 description 13
- 238000006243 chemical reaction Methods 0.000 description 10
- 208000000810 Separation Anxiety Diseases 0.000 description 7
- 208000035475 disorder Diseases 0.000 description 7
- 241000894007 species Species 0.000 description 7
- 238000002560 therapeutic procedure Methods 0.000 description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 102100024304 Protachykinin-1 Human genes 0.000 description 5
- 102000003141 Tachykinin Human genes 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- 230000009191 jumping Effects 0.000 description 5
- 108060008037 tachykinin Proteins 0.000 description 5
- 229940079593 drug Drugs 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 238000009987 spinning Methods 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- QDZOEBFLNHCSSF-PFFBOGFISA-N (2S)-2-[[(2R)-2-[[(2S)-1-[(2S)-6-amino-2-[[(2S)-1-[(2R)-2-amino-5-carbamimidamidopentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-3-(1H-indol-3-yl)propanoyl]amino]-N-[(2R)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]pentanediamide Chemical compound C([C@@H](C(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CCCNC(N)=N)C1=CC=CC=C1 QDZOEBFLNHCSSF-PFFBOGFISA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 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
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 3
- 101800003906 Substance P Proteins 0.000 description 3
- 238000003556 assay Methods 0.000 description 3
- 230000003542 behavioural effect Effects 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 239000008121 dextrose Substances 0.000 description 3
- 239000003085 diluting agent Substances 0.000 description 3
- 230000008030 elimination Effects 0.000 description 3
- 238000003379 elimination reaction Methods 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 238000010254 subcutaneous injection Methods 0.000 description 3
- 239000007929 subcutaneous injection Substances 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 206010000117 Abnormal behaviour Diseases 0.000 description 2
- 206010001488 Aggression Diseases 0.000 description 2
- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
- 241000282465 Canis Species 0.000 description 2
- GDLIGKIOYRNHDA-UHFFFAOYSA-N Clomipramine Chemical compound C1CC2=CC=C(Cl)C=C2N(CCCN(C)C)C2=CC=CC=C21 GDLIGKIOYRNHDA-UHFFFAOYSA-N 0.000 description 2
- 229920000858 Cyclodextrin Polymers 0.000 description 2
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- 101000831616 Homo sapiens Protachykinin-1 Proteins 0.000 description 2
- GIYXAJPCNFJEHY-UHFFFAOYSA-N N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-1-propanamine hydrochloride (1:1) Chemical compound Cl.C=1C=CC=CC=1C(CCNC)OC1=CC=C(C(F)(F)F)C=C1 GIYXAJPCNFJEHY-UHFFFAOYSA-N 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- 206010039424 Salivary hypersecretion Diseases 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 206010044565 Tremor Diseases 0.000 description 2
- 208000012761 aggressive behavior Diseases 0.000 description 2
- 230000016571 aggressive behavior Effects 0.000 description 2
- KRMDCWKBEZIMAB-UHFFFAOYSA-N amitriptyline Chemical compound C1CC2=CC=CC=C2C(=CCCN(C)C)C2=CC=CC=C21 KRMDCWKBEZIMAB-UHFFFAOYSA-N 0.000 description 2
- 208000022531 anorexia Diseases 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 238000009227 behaviour therapy Methods 0.000 description 2
- 229960004606 clomipramine Drugs 0.000 description 2
- 230000001186 cumulative effect Effects 0.000 description 2
- 206010061428 decreased appetite Diseases 0.000 description 2
- 201000010099 disease Diseases 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 239000002552 dosage form Substances 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 235000013305 food Nutrition 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000002674 ointment Substances 0.000 description 2
- 238000007911 parenteral administration Methods 0.000 description 2
- 125000001151 peptidyl group Chemical group 0.000 description 2
- 229940001470 psychoactive drug Drugs 0.000 description 2
- 239000004089 psychotropic agent Substances 0.000 description 2
- 208000026451 salivation Diseases 0.000 description 2
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 238000007790 scraping Methods 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- ADNPLDHMAVUMIW-CUZNLEPHSA-N substance P Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 ADNPLDHMAVUMIW-CUZNLEPHSA-N 0.000 description 2
- 239000003826 tablet Substances 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 238000004448 titration Methods 0.000 description 2
- 238000012549 training Methods 0.000 description 2
- 238000012546 transfer Methods 0.000 description 2
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 1
- 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 description 1
- GRBSRKIQJCLYFU-WNJJXGMVSA-N 1-(4-fluorophenyl)-4-[(2s,3s)-3-[(2-methoxyphenyl)methylamino]-2-phenylpiperidin-1-yl]butan-1-one Chemical compound COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)N(CCCC(=O)C=2C=CC(F)=CC=2)CCC1 GRBSRKIQJCLYFU-WNJJXGMVSA-N 0.000 description 1
- GLQPTZAAUROJMO-UHFFFAOYSA-N 4-(3,4-dimethoxyphenyl)benzaldehyde Chemical compound C1=C(OC)C(OC)=CC=C1C1=CC=C(C=O)C=C1 GLQPTZAAUROJMO-UHFFFAOYSA-N 0.000 description 1
- HQZONHWUUKPDRH-QGWOSTIUSA-N 4-[(2s,3s)-3-[(2-methoxyphenyl)methylamino]-2-phenylpiperidin-1-yl]-1-phenylbutan-1-ol Chemical compound COC1=CC=CC=C1CN[C@@H]1[C@H](C=2C=CC=CC=2)N(CCCC(O)C=2C=CC=CC=2)CCC1 HQZONHWUUKPDRH-QGWOSTIUSA-N 0.000 description 1
- HGPNOJKZSWSOKK-XYOGLKKJSA-N CC(C)NC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(C)C.CC(N=C(C)S1)=C1S(O)(=O)=O Chemical compound CC(C)NC(C=C1)=CC(CN[C@@H]2[C@H](C3=CC=CC=C3)NCCC2)=C1OC(C)C.CC(N=C(C)S1)=C1S(O)(=O)=O HGPNOJKZSWSOKK-XYOGLKKJSA-N 0.000 description 1
- 241000824799 Canis lupus dingo Species 0.000 description 1
- 208000006561 Cluster Headache Diseases 0.000 description 1
- 206010009900 Colitis ulcerative Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 206010012735 Diarrhoea Diseases 0.000 description 1
- PIICEJLVQHRZGT-UHFFFAOYSA-N Ethylenediamine Chemical compound NCCN PIICEJLVQHRZGT-UHFFFAOYSA-N 0.000 description 1
- 206010015548 Euthanasia Diseases 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 239000004705 High-molecular-weight polyethylene Substances 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020710 Hyperphagia Diseases 0.000 description 1
- 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 1
- 206010024264 Lethargy Diseases 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 102400000097 Neurokinin A Human genes 0.000 description 1
- 101800000399 Neurokinin A Proteins 0.000 description 1
- HEAUFJZALFKPBA-YRVBCFNBSA-N Neurokinin A Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCCN)NC(=O)[C@@H](N)CC=1NC=NC=1)C(C)O)C1=CC=CC=C1 HEAUFJZALFKPBA-YRVBCFNBSA-N 0.000 description 1
- 102000046798 Neurokinin B Human genes 0.000 description 1
- NHXYSAFTNPANFK-HDMCBQFHSA-N Neurokinin B Chemical compound C([C@@H](C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(N)=O)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCSC)NC(=O)[C@@H](N)CC(O)=O)C1=CC=CC=C1 NHXYSAFTNPANFK-HDMCBQFHSA-N 0.000 description 1
- 101800002813 Neurokinin-B Proteins 0.000 description 1
- 108090000189 Neuropeptides Proteins 0.000 description 1
- 208000008589 Obesity Diseases 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 208000004880 Polyuria Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 208000025747 Rheumatic disease Diseases 0.000 description 1
- 244000000231 Sesamum indicum Species 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 208000032140 Sleepiness Diseases 0.000 description 1
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 206010041349 Somnolence 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
- 102000007124 Tachykinin Receptors Human genes 0.000 description 1
- 108010072901 Tachykinin Receptors Proteins 0.000 description 1
- 229940123445 Tricyclic antidepressant Drugs 0.000 description 1
- 201000006704 Ulcerative Colitis Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- NOSIYYJFMPDDSA-UHFFFAOYSA-N acepromazine Chemical compound C1=C(C(C)=O)C=C2N(CCCN(C)C)C3=CC=CC=C3SC2=C1 NOSIYYJFMPDDSA-UHFFFAOYSA-N 0.000 description 1
- 229960005054 acepromazine Drugs 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 239000000783 alginic acid Substances 0.000 description 1
- 235000010443 alginic acid Nutrition 0.000 description 1
- 229920000615 alginic acid Polymers 0.000 description 1
- 229960001126 alginic acid Drugs 0.000 description 1
- 150000004781 alginic acids Chemical class 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229960000836 amitriptyline Drugs 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 229940005513 antidepressants Drugs 0.000 description 1
- 230000010397 anxiety-related behavior Effects 0.000 description 1
- 239000002249 anxiolytic agent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 231100000871 behavioral problem Toxicity 0.000 description 1
- 238000013542 behavioral therapy Methods 0.000 description 1
- 229940049706 benzodiazepine Drugs 0.000 description 1
- 150000001557 benzodiazepines Chemical class 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 229960002495 buspirone Drugs 0.000 description 1
- QWCRAEMEVRGPNT-UHFFFAOYSA-N buspirone Chemical compound C1C(=O)N(CCCCN2CCN(CC2)C=2N=CC=CN=2)C(=O)CC21CCCC2 QWCRAEMEVRGPNT-UHFFFAOYSA-N 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 229960003563 calcium carbonate Drugs 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 210000003169 central nervous system Anatomy 0.000 description 1
- 208000015114 central nervous system disease Diseases 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 208000018912 cluster headache syndrome Diseases 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 238000011284 combination treatment Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 239000006071 cream Substances 0.000 description 1
- 238000000586 desensitisation Methods 0.000 description 1
- 230000001066 destructive effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 229960003529 diazepam Drugs 0.000 description 1
- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 229940095079 dicalcium phosphate anhydrous Drugs 0.000 description 1
- 239000007884 disintegrant Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 229960002464 fluoxetine Drugs 0.000 description 1
- 229960000389 fluoxetine hydrochloride Drugs 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000007903 gelatin capsule Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 229960002449 glycine Drugs 0.000 description 1
- 230000035929 gnawing Effects 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 235000015110 jellies Nutrition 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 239000007937 lozenge Substances 0.000 description 1
- 239000000314 lubricant Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000001404 mediated effect Effects 0.000 description 1
- CWWARWOPSKGELM-SARDKLJWSA-N methyl (2s)-2-[[(2s)-2-[[2-[[(2s)-2-[[(2s)-2-[[(2s)-5-amino-2-[[(2s)-5-amino-2-[[(2s)-1-[(2s)-6-amino-2-[[(2s)-1-[(2s)-2-amino-5-(diaminomethylideneamino)pentanoyl]pyrrolidine-2-carbonyl]amino]hexanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-5 Chemical compound C([C@@H](C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)OC)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CCCN=C(N)N)C1=CC=CC=C1 CWWARWOPSKGELM-SARDKLJWSA-N 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000012544 monitoring process Methods 0.000 description 1
- 239000013642 negative control Substances 0.000 description 1
- 239000002742 neurokinin 1 receptor antagonist Substances 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 229960002748 norepinephrine Drugs 0.000 description 1
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 1
- 235000020824 obesity Nutrition 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000008203 oral pharmaceutical composition Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 230000007310 pathophysiology Effects 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000008177 pharmaceutical agent Substances 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000008024 pharmaceutical diluent Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 150000002990 phenothiazines Chemical class 0.000 description 1
- 150000004885 piperazines Chemical class 0.000 description 1
- 206010036067 polydipsia Diseases 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 208000022530 polyphagia Diseases 0.000 description 1
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- 229940035613 prozac Drugs 0.000 description 1
- SBYHFKPVCBCYGV-UHFFFAOYSA-N quinuclidine Chemical compound C1CC2CCN1CC2 SBYHFKPVCBCYGV-UHFFFAOYSA-N 0.000 description 1
- 150000008584 quinuclidines Chemical class 0.000 description 1
- 238000001525 receptor binding assay Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000000241 respiratory effect Effects 0.000 description 1
- 208000023504 respiratory system disease Diseases 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 229940124834 selective serotonin reuptake inhibitor Drugs 0.000 description 1
- 239000012896 selective serotonin reuptake inhibitor Substances 0.000 description 1
- 239000003772 serotonin uptake inhibitor Substances 0.000 description 1
- VGKDLMBJGBXTGI-SJCJKPOMSA-N sertraline Chemical compound C1([C@@H]2CC[C@@H](C3=CC=CC=C32)NC)=CC=C(Cl)C(Cl)=C1 VGKDLMBJGBXTGI-SJCJKPOMSA-N 0.000 description 1
- 229960003660 sertraline hydrochloride Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 150000004760 silicates Chemical class 0.000 description 1
- 230000037321 sleepiness Effects 0.000 description 1
- 239000001509 sodium citrate Substances 0.000 description 1
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 description 1
- 229960001790 sodium citrate Drugs 0.000 description 1
- 235000011083 sodium citrates Nutrition 0.000 description 1
- 235000019333 sodium laurylsulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 230000002269 spontaneous effect Effects 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 230000001629 suppression Effects 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000012222 talc Nutrition 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 239000003029 tricyclic antidepressant agent Substances 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- PNVNVHUZROJLTJ-UHFFFAOYSA-N venlafaxine Chemical compound C1=CC(OC)=CC=C1C(CN(C)C)C1(O)CCCCC1 PNVNVHUZROJLTJ-UHFFFAOYSA-N 0.000 description 1
- 229960004688 venlafaxine Drugs 0.000 description 1
- 230000008673 vomiting Effects 0.000 description 1
- DYWSVUBJGFTOQC-UHFFFAOYSA-N xi-2-Ethylheptanoic acid Chemical compound CCCCCC(CC)C(O)=O DYWSVUBJGFTOQC-UHFFFAOYSA-N 0.000 description 1
- 229940020965 zoloft Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/454—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
-
- 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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4418—Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
-
- 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
- A61K31/46—8-Azabicyclo [3.2.1] octane; Derivatives thereof, e.g. atropine, cocaine
-
- 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
- A61K31/47—Quinolines; Isoquinolines
- A61K31/49—Cinchonan derivatives, e.g. quinine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/22—Anxiolytics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Landscapes
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Emergency Medicine (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Hydrogenated Pyridines (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US30669201P | 2001-07-20 | 2001-07-20 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CZ200434A3 true CZ200434A3 (cs) | 2005-02-16 |
Family
ID=23186426
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CZ200434A CZ200434A3 (cs) | 2001-07-20 | 2002-07-15 | Léčivo pro léčení abnormálního úzkosného chování u domácích zvířat a způsob screeningu zkoušené sloučeniny za účelem stanovení anxiolytické účinnosti u psů |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US20030139443A1 (https=) |
| EP (1) | EP1411946A1 (https=) |
| JP (1) | JP2005504029A (https=) |
| KR (1) | KR20040029375A (https=) |
| CN (1) | CN1529600A (https=) |
| CA (1) | CA2448722A1 (https=) |
| CZ (1) | CZ200434A3 (https=) |
| HU (1) | HUP0401154A2 (https=) |
| IL (1) | IL158990A0 (https=) |
| PL (1) | PL367944A1 (https=) |
| SK (1) | SK252004A3 (https=) |
| WO (1) | WO2003009848A1 (https=) |
| ZA (1) | ZA200308991B (https=) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2554823A1 (en) | 2004-01-30 | 2005-09-09 | Pfizer Products Inc. | Nk-1 receptor antagonists to improve anesthesia recovery |
| LT1713504T (lt) | 2004-01-30 | 2017-09-11 | Zoetis Services Llc | Antimikrobinis konservantas, skirtas multi-dozinėms kompozicijoms, panaudojant beta-ciklodekstrinus, skirtas skystoms vaisto formoms |
| CA2564751A1 (en) * | 2004-04-30 | 2005-11-24 | Schering Corporation | Neuropeptide receptor modulators |
| CN114403042A (zh) * | 2021-12-13 | 2022-04-29 | 深圳先进技术研究院 | 一种大动物焦虑症动物模型 |
Family Cites Families (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX18467A (es) * | 1988-11-23 | 1993-07-01 | Pfizer | Agentes terapeuticos de quinuclidinas |
| US5232929A (en) * | 1990-11-28 | 1993-08-03 | Pfizer Inc. | 3-aminopiperidine derivatives and related nitrogen containing heterocycles and pharmaceutical compositions and use |
| FR2677361A1 (fr) * | 1991-06-04 | 1992-12-11 | Adir | Nouveaux peptides et pseudopeptides, derives de tachykinines, leur procede de preparation et les compositions pharmaceutiques qui les contiennent. |
| AU657552B2 (en) * | 1991-05-31 | 1995-03-16 | Pfizer Inc. | Quinuclidine as substance P antagonists |
| DE69213451T2 (de) * | 1991-06-20 | 1997-01-09 | Pfizer Inc., New York | Fluoralkoxybenzylaminoderivate stickstoffhaltiger heterocyclen |
| ATE166650T1 (de) * | 1993-03-04 | 1998-06-15 | Pfizer | Spiroazacyclischderivate als substanz p antagonisten |
| DK0623344T3 (da) * | 1993-05-04 | 2000-12-18 | Ceva Sante Animale | Anvendelse af selegilin i veterinær medicin |
| IL109646A0 (en) * | 1993-05-19 | 1994-08-26 | Pfizer | Heteroatom substituted alkyl benzylamino-quinuclidines |
| US5393762A (en) * | 1993-06-04 | 1995-02-28 | Pfizer Inc. | Pharmaceutical agents for treatment of emesis |
| US6083943A (en) * | 1993-09-17 | 2000-07-04 | Pfizer Inc | Substituted azaheterocyclecarboxylic acid |
| EP1209157A1 (en) * | 1993-09-17 | 2002-05-29 | Pfizer Inc. | Heteroarylamino and heteroarylsulfonamido substituted 3-benzylaminomethyl piperidines and related compounds |
| US5854262A (en) * | 1993-10-07 | 1998-12-29 | Pfizer Inc. | Aminomethylene substituted non-aromatic heterocycles and use as substance P antagonists |
| PE45195A1 (es) * | 1994-03-03 | 1996-01-17 | Boehringer Ingelheim Kg | Derivado de aminoacido, procedimiento para su preparacion y composicion farmaceutica que lo contiene |
| US5607936A (en) * | 1994-09-30 | 1997-03-04 | Merck & Co., Inc. | Substituted aryl piperazines as neurokinin antagonists |
| ES2229259T3 (es) * | 1995-01-12 | 2005-04-16 | Glaxo Group Limited | Derivados de piperidina con actividad antagonista de taquiquinina. |
| US5990125A (en) * | 1996-01-19 | 1999-11-23 | Pfizer Inc. | NK-1 receptor antagonists for the treatment of cancer |
| US6117855A (en) * | 1996-10-07 | 2000-09-12 | Merck Sharp & Dohme Ltd. | Use of a NK-1 receptor antagonist and an antidepressant and/or an anti-anxiety agent |
| DE69736390T2 (de) * | 1996-10-07 | 2007-07-26 | Merck Sharp & Dohme Ltd., Hoddesdon | Zns-penetrierende nk-1 rezeptorantagonisten als antidepressivum und / oder anxiolytikum |
| IL130223A (en) * | 1996-12-19 | 2005-09-25 | Aventis Pharma Inc | Heterocyclic substituted pyrrolidine amide derivatives, process for their preparation and pharmaceutical compositions containing them |
| US6156749A (en) * | 1997-12-01 | 2000-12-05 | Merck Sharp & Dohme Limited | Use of NK-1 receptor antagonists for treating movement disorders |
| JP4669095B2 (ja) * | 1999-07-19 | 2011-04-13 | 太陽化学株式会社 | ペットの問題行動抑制組成物 |
| CA2280309C (en) * | 1999-08-13 | 2007-05-08 | William Norton Milgram | Use of adrafinil to treat behavioral problems in aged canines |
| CA2324813A1 (en) * | 1999-11-10 | 2001-05-10 | Susan Beth Sobolov-Jaynes | Combination treatment for depression and anxiety |
| US20020049211A1 (en) * | 2000-09-06 | 2002-04-25 | Sobolov-Jaynes Susan Beth | Combination treatment for depression and anxiety |
-
2002
- 2002-07-15 PL PL02367944A patent/PL367944A1/xx not_active Application Discontinuation
- 2002-07-15 WO PCT/IB2002/002847 patent/WO2003009848A1/en not_active Ceased
- 2002-07-15 CN CNA028141873A patent/CN1529600A/zh active Pending
- 2002-07-15 JP JP2003515240A patent/JP2005504029A/ja not_active Withdrawn
- 2002-07-15 IL IL15899002A patent/IL158990A0/xx unknown
- 2002-07-15 KR KR10-2004-7000901A patent/KR20040029375A/ko not_active Ceased
- 2002-07-15 HU HU0401154A patent/HUP0401154A2/hu unknown
- 2002-07-15 SK SK25-2004A patent/SK252004A3/sk not_active Application Discontinuation
- 2002-07-15 CZ CZ200434A patent/CZ200434A3/cs unknown
- 2002-07-15 EP EP02745741A patent/EP1411946A1/en not_active Withdrawn
- 2002-07-15 CA CA002448722A patent/CA2448722A1/en not_active Abandoned
- 2002-07-19 US US10/199,284 patent/US20030139443A1/en not_active Abandoned
-
2003
- 2003-11-19 ZA ZA200308991A patent/ZA200308991B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| PL367944A1 (en) | 2005-03-07 |
| CN1529600A (zh) | 2004-09-15 |
| IL158990A0 (en) | 2004-05-12 |
| HUP0401154A2 (hu) | 2004-10-28 |
| CA2448722A1 (en) | 2003-02-06 |
| JP2005504029A (ja) | 2005-02-10 |
| EP1411946A1 (en) | 2004-04-28 |
| KR20040029375A (ko) | 2004-04-06 |
| US20030139443A1 (en) | 2003-07-24 |
| ZA200308991B (en) | 2004-11-19 |
| SK252004A3 (sk) | 2005-03-04 |
| WO2003009848A1 (en) | 2003-02-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Robichaud et al. | PDE4 inhibitors induce emesis in ferrets via a noradrenergic pathway | |
| Mohammad‐Zadeh et al. | Serotonin: a review | |
| US10632116B2 (en) | Combinations of serotonin receptor agonists for treatment of movement disorders | |
| Ogata¹ et al. | Selective serotonin reuptake inhibitors | |
| JP2001523245A (ja) | 肥満を治療するためのｎｋ−１受容体拮抗薬およびｓｓｒｉの使用 | |
| Fibiger et al. | A biphasic action of central cholinergic stimulation on behavioral arousal in the rat | |
| JPH08225464A (ja) | 嘔吐治療用ｎｋ−１受容体アンタゴニスト及び５ｈｔ３受容体アンタゴニスト | |
| AU774117B2 (en) | The use of certain affinity NMDA antagonists as antidepressants | |
| EP3897641B1 (en) | Treatment of movement disorders | |
| JP2005533080A (ja) | Ｎｋ−１およびｎｋ−３アンタゴニストによる鬱病および不安症の併用療法 | |
| US20140221385A1 (en) | Combinations of serotonin receptor agonists for treatment of movement disorders | |
| JP2009518423A (ja) | 統合失調症の副作用および陰性症状を治療するためのｃｂ１アンタゴニストの使用 | |
| US20080194631A1 (en) | Medicament For the Treatment of Central Nervous System Disorders | |
| CZ200434A3 (cs) | Léčivo pro léčení abnormálního úzkosného chování u domácích zvířat a způsob screeningu zkoušené sloučeniny za účelem stanovení anxiolytické účinnosti u psů | |
| US4468391A (en) | Combination of β-adrenoceptor antagonists and anxiolytic agents | |
| DE102004063753A1 (de) | Verwendung ausgewählter CGRP-Antagonisten in Kombination mit anderen Arzneistoffen gegen Migräne für die Behandlung von Migräne | |
| CA2994150A1 (en) | Antitussive compositions and methods | |
| Landsberg | Clomipramine--beyond separation anxiety | |
| US6511982B2 (en) | Treatment of pain | |
| CZ20031433A3 (cs) | Nové použití kombinovaných 5-HT1A agonistů a inhibitorů reabsorpce serotoninu | |
| AU2002317436A1 (en) | Use of NK-1 receptor antagonists to modify unwanted behaviour in dogs, cats and horses | |
| Gruen et al. | Drugs affecting animal behavior | |
| JP2005504029A5 (https=) | ||
| JP2019516758A (ja) | 不安障害を治療するための（２Ｓ）−１−［４−（３，４−ジクロロフェニル）ピペリジン−１−イル］−３−［２−（５−メチル−１，３，４−オキサジアゾール−２−イル）ベンゾ［ｂ］フラン−４−イルオキシ］プロパン−２−オールまたはその代謝産物 | |
| CA2188227C (en) | Combination antiemetic therapy using nk-1 receptor antagonists |