Inhibition of 3H-clozapine binding in rat brain after oral administration of neuroleptics

Clozapine, thioridazine, perlapine, clothiapine, chlorpromazine, NT 104–252, loxapine or haloperidol were administered orally, and atropine subcutaneously, to rats. The animals were decapitated, brain tissue was removed and homogenized in tris buffer and incubated with ³H-clozapine. Total and nonspecifically bound ³H-clozapine were measured in each preparation. A dose-dependent inhibition of specific ³H-clozapine binding of more than 50% was observed only after the administration of clozapine or thioridazine. There was no correlation between inhibition of ³H-clozapine binding and that of ³H-haloperidol, a specific ligand for DA-receptors. ³H-Clozapine receptor density was much greater than ³H-haloperidol receptor density, suggesting that the majority of clozapine binding sites are not DA-receptors.