Binding of typical and atypical antipsychotics to 5-HT1C and 5-HT2 sites: clozapine potently interacts with 5-HT1C sites.
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.
Canton
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H
Neurobiology Division, FONDAX-Groupe de Recherche Servier, Puteaux, France.
Verrièle
L
L
Colpaert
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FC
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
D014150:Antipsychotic Agents; D004873:Ergolines; D011985:Receptors, Serotonin; D007650:Ketanserin; D003024:Clozapine; C031649:mesulergine