CHARACTERIZATION OF [H-3] CLOZAPINE BINDING-SITES IN RAT-BRAIN

We examined the characteristics of [H-3]clozapine binding sites in fou r rat brain regions (frontal cortex, limbic area, hippocampus and stri atum) in order to elucidate the pharmacological profile of this unique atypical antipsychotic drug. The specific [H-3]clozapine binding was found to be saturable and reversible in all these brain regions. Scatc hard analysis of the saturation data indicated that the specific bindi ng consisted of high- and low-affinity components. Displacement experi ments showed that the muscarinic cholinergic receptor represented abou t 50% of [H-3]clozapine binding in each brain area. Serotonin 5-HT2 an d dopamine D-4 receptor binding sites could also be detected by displa cement experiments using ketanserin and nemonapride, respectively, in frontal cortex and limbic area, but not in hippocampus or striatum. Al pha-1, alpha-2, histamine H-1, dopamine D-1, D-2, or D-3 receptor comp onents could not be determined within the high-affinity [H-3]clozapine binding sites in any brain region. It is possible that the atypical p roperty of clozapine may depend on the modulatory effect on dopaminerg ic function via 5-HT2 receptor blockade and/or may be mediated via D-4 receptor blockade in the mesocortical and mesolimbic area.