Anti-cataleptic effects of clozapine, but not olanzapine and quetiapine, on SCH 23390- or raclopride-induced catalepsy in rats

The present study investigated potential anti-cataleptic properties of the prototype atypical antipsychotic clozapine and two newly developed atypical antipsychotics, olanzapine and quetiapine, which are structurally related and display similar pharmacological profiles to clozapine. Clozapine (2.5 mg kg^-1, s.c.), but not olanzapine (2.0 mg kg^-1, s.c.) and quetiapine (20.0 mg kg^-1, s.c.), blocked catalepsy induced either by the dopamine D_1/5 receptor antagonist SCH 23390 (50.0 μg kg^-1, s.c) or the selective dopamine D_2/3 receptor antagonist raclopride (4.0 mg kg^-1, s.c.). Such findings are consistent with the beneficial effects of clozapine in the management of drug-induced psychosis in parkinsonian patients, and suggest that neither olanzapine nor quetiapine may be a safe alternative to clozapine in this field. Furthermore, the results indicate that clozapine has a unique pharmacological profile that distinguishes it from olanzapine and quetiapine. The mechanisms underlying anti-cataleptic or anti-parkinsonian properties of clozapine are unclear but may be related to dopamine D₁ receptor agonism of clozapine.