- Combination treatment for anxiety, depression, obsessive compulsive disorder and psychosis
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The present invention relates to a method of treating depression, obsessive compulsive disorder and psychosis in a mammal, including a human, by administering to the mammal an atypical antipsychotic in combination with an antidepressant agent with improvement in efficiency. It also relates to pharmaceutical compositions containing a pharmaceutically acceptable carrier, an atypical antipsychotic, and an SRI.
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- Process for the preparation of 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole and method of manufacturing sertindole
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A process of manufacturing sertindole comprising reacting 5-chloro-1-(4-fluorophenyl)indole with 4-piperidone in a mixture of an acetic acid and concentrated HCl; reduction of the resulting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridin-4-yl)indole and reaction of this compound with 1-(2-chloroethyl)-2-imidazolidinon in order to obtain sertindole.
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- Noncataleptogenic, centrally acting dopamine D-2 and serotonin 5-HT2 antagonists within a series of 3-substituted 1-(4-fluorophenyl)-1H-indoles
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A series of 1-(4-fluorophenyl)-1H-indoles substituted at the 3-position with 1-piperazinyl, 1,2,3,6-tetrahydro-4-pyridinyl, and 4-piperidinyl was synthesized. Within all three subseries potent dopamine D-2 and serotonin 5- HT2 receptor affinity was found in ligand binding studies. Quipazine-induced head twitches in rats were inhibited by most derivatives as a measure of central 5-HT2 receptor antagonism. Piperazinyl and tetrahydropyridyl indoles were cataleptogenic, while piperidyl substituted indoles surprisingly were found to be noncataleptogenic or only weakly cataleptogenic. Noncataleptogenic piperidyl derivatives also failed to block dopaminergic- mediated stereotypies, that is methyl phenidate-induced gnawing behavior in mice. These profiles resemble that of the atypical neuroleptic clozapine. 1- Ethyl-2-imidazolidinone was found to be the optimal substituent of the basic nitrogen atom in order to avoid catalepsy. The atypical neuroleptic 1-[2-[4- [5-chloro-1-(4-fluorophenyl)-1H-indol-3-yl]-1-piperidinyl]ethyl]-2- imidazolidinone (sertindole, compound 14c) was selected for further development as a result of these structure/activity studies.
- Perregaard,Arnt,Bogeso,Hyttel,Sanchez
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p. 1092 - 1101
(2007/10/02)
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