Pharmaceutical composition for treating and/or preventing a pathology associated with an obsessional behavior or with obesity
View Patent ↗This invention relates to the use of a ligand of the 5-HT 4 receptor or of a pharmaceutically acceptable salt of this ligand and to a nucleic acid coding for a 5-HT 4 receptor or of a functionally equivalent receptor for a drug for treating and/or preventing a pathology associated with an obsessional behavior such as anorexia, bulimia and the addiction to drugs of abuse or obesity. The invention also relates to a method for identifying a compound that is biologically active in the treatment and/or the prevention of a pathology associated with an obsessional conduct or obesity including: a) placing the 5-HT 4 receptor or a functionally equivalent receptor in contact with this biologically active compound, and b) the determination of whether this biologically active compound is capable of modulating the basal activity of the 5-HT 4 receptor or of a functionally equivalent receptor.
1. A method of treating a pathology associated with an obsessional behavior of a mammal in need thereof, wherein the pathology is anorexia, the method comprising administering a therapeutically effective amount of an antagonist of a 5-HT 4 receptor, an inverse agonist of a 5-HT 4 receptor, a pharmaceutically acceptable salt of the antagonist, or a pharmaceutically acceptable salt of the inverse agonist to the mammal to treat the mammal.
2. The method of claim 1 , wherein an antagonist is administered.
3. The method of claim 2 , wherein the antagonist is selected from the group consisting of
tropisetron (ICS 205 930; [(3a tropanyl)-1H-indole-3-carboxylic acid ester]),
RS 100235 (1-(8-amino-7-chloro-1,4-benzodioxan-5-yl)-3-[[3,4-dimethoxyphenyl)prop-1-yl]piperidine-4-yl]propan-1-one,
A-85380 (3-(2(S)-azetidinylmethoxy)pyridine),
GR 113808 (1-[2-(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl 1-methyl-1H-indole-3-carboxylate),
GR 125487 (1-[2-(methylsulphonyl)amino]ethyl]-4-piperidinyl]methyl-5-fluoro-2-methoxy-1H-indole-3-carboxylate),
GR 138897 ([1-[2-[methylsulphonyl)amino]-4-piperidinyl]methyl[2-(3-methyl-1,2,4-oxa-diazon-5-yl)phenyl]carbamate],
SB 203186(1-piperidinyl)ethyl 1H-indole 3-carboxylate),
SDZ 205-557 (2-methyox-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester hydrochloride),
LY 353433 (1-(1-methylethyl)-N-(2-(4-((tricyclo[2-(3.3.1.1 3 ,7]dec-1-ylcarbonyl)amino-1-piperidinyl)ethyl)-1H-indazole-3-carboxamide),
RS 23597 (3-piperidine-1-yl)propyl-4-amino-5-chloro-2-methoxybenzoate hydrochloride),
SB 204070 (1-butyl-4-piperidinyl)methyl 8-amino-7-chloro-1,4-benzodioxan-5-carboxylate),
DAU 6285 ((endo-6-methoxy-8-methyl-8-azabicyclo[3.2.1]oct3-yl)-2,3-dihydro-2-oxo-1-H-benzimidazole-1 carboxylate hydrochloride),
SC53606 ((1-S,8-S)—N-[hexahydro-1H-pyrrolizin-1-yl)methyl]-6-chloroimidazo[1,2-a]pyridine-8-carboxamide hydrochloride),
RS67532 (1-(4-amino-5-chloro-2-(3,5-dimethoxy benzyloxyphenyl)-5-(1-piperidinyl)-1-pentanone),
SB 207266 (N-[1-.sup.nbutyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a]indole-10-carboxamide),
RS 39604 (1-[4-amino-5-chloro-2-(3,5-dimethoxyphenyl)methyloxy]-3-[1[2-methylsulphonylamino]ethyl]piperidine-4-yl]propan-1-one),
RS 1003002 (N-2-(4-(3-(8-amino-7-chloro-2,3-dihydro-1,4-benzodioxin-5-yl)-3-oxopropyl)piperidin-1-yl)ethyl)-methanesulfonamide),
ML 10375 (2-cis-3,5-dimethylpiperidino)ethyl 4-amino-5-chloro2 methoxybenzoate),
SB 207710 (1-butyl-4-piperidinyl)methyl-8-amino-7-1,4-benzodioxan-5-carboxylate),
SB205800 (N-(1-butyl-4-piperidinyl)methyl-8-amino-7-chloro-1,4-benzodioxan-5-carboxamide),
N 3389 (N-[(1S,5R)-3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-yl]-1H-indazole-3-carboxamide dihydrochloride),
and
R 50595 (4-amino-N-[(3S,4R)-1-[4,4-bis(4-fluorophenyl)butyl]-3-methoxypiperidin-4-yl]-5-chloro-2-methoxybenzamide hydrochloride).
4. The method of claim 1 , wherein an inverse agonist is administered.
5. The method of claim 4 , wherein the inverse agonist is selected from the group consisting of
(1-butylpiperidin-4-yl)methyl 2,3-dihydro-1,4-benzodioxine-8-carboxylate (RO 116-0086), and
N-[(1-butylpiperidin-4-yl)methyl]-2,3-dihydro-1,4-benzodioxine-5-carboxamide (RO 116-1148).
6. The method of claim 1 , wherein the mammal is a human.