title: Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites.
abstract: We determined the affinity of several typical and atypical antipsychotics for the 5-HT1C and 5-HT2 sites using radioligand binding assays. Most of the antipsychotics tested appeared to bind to 5-HT2 sites with affinities that were fairly high (i.e. pKi values between 7 and 9) and significantly higher than for 5-HT1C sites. In contrast, clozapine was found to have a significantly higher affinity for 5-HT1C than for 5-HT2 sites. Clozapine had the highest affinity for 5-HT1C sites of all the compounds tested. These findings are consistent with the hypothesis that an interaction with 5-HT2 receptors may be relevant to the clinical activity of typical antipsychotics. The findings also suggest, however, that an interaction with 5-HT1C sites may be relevant to the mechanism of clinical action of clozapine and, perhaps, of other atypical antipsychotics.
authors.affiliation: Neurobiology Division, FONDAX-Groupe de Recherche Servier, Puteaux, France.
authors.forename: H
authors.initials: H
authors.lastname: Canton
authors.forename: L
authors.initials: L
authors.lastname: Verrièle
authors.forename: F C
authors.initials: FC
authors.lastname: Colpaert
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001665:Binding Sites; D002831:Choroid Plexus / Q000378:metabolism; D003024:Clozapine / Q000378:metabolism*; D004873:Ergolines / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D007700:Kinetics; D011985:Receptors, Serotonin / Q000145:classification / Q000378:metabolism*; D013552:Swine
chemical_list: D014150:Antipsychotic Agents; D004873:Ergolines; D011985:Receptors, Serotonin; D007650:Ketanserin; D003024:Clozapine; C031649:mesulergine