Detection of the nueroleptic properties of clozapine, sulpiride and thioridazine

Abstract

The cataleptic and antistereotypic abilities of clozapine, sulpiride and thioridazine were determined in the rat and compared with the responses of typical neuroleptic agents, haloperidol, fluphenazine and pimozide. Haloperidol and fluphenazine caused a dose-dependent cataleptic state which attained maximum intensity: the effects of pimozide were also dose-dependent but, although the catalepsy was marked, maximum intensity was not attained. In contrast, thioridazine, clozapine and sulpiride each caused a very weak, but definite, cataleptic response although a dose-dependency could not be demonstrated. Pretreatment of animals with alpha-methylparatyrosine was shown to significantly potentiate the cataleptic actions of haloperidol, fluphenazine, pimozide, thioridazine and sulpiride but failed to modify the action of clozapine, Threshold cataleptic doses of all agents markedly synergised in the production of catalepsy with threshold doses of the cholinergic drug RS86. Similarly, all "neuroleptic" agents tested were shown to reduce the intensity of the stereotyped behaviour induced by amphetamine, apomorphine and nomifensine in a dose-dependent manner but only haloperidol, fluphenazine and pimozide were shown to be capable of 100% inhibition. The antistereotypic abilities of haloperidol, fluphenazine and pimozide were most marked against amphetamine, but this was not a consistent observation for thioridazine, clozapine and sulpiride. Threshold, or even subthreshold, doses of both the typical and atypical neuroleptic agents combined with threshold doses of RS86 markedly synergised in the antagonism of the stereotypic actions of amphetamine, apomorphine and nomifensine.