CLOZAPINE INHIBITS CATALEPSY INDUCED BY OLANZAPINE AND LOXAPINE, BUT PROLONGS CATALEPSY INDUCED BY SCH-23390 IN RATS

Loxapine (0.3 mg/kg s.c.), olanzapine (10 mg/kg s.c.) and SCH 23390 (R -(+)-chloro-2, 3, 4, 5-tetrahydro-3-methyl-5-phenyl- 1-H-3-benzazepine ; 1 mg/kg, s.c.), but not clozapine (10 mg/kg, s.c.), induced cataleps y in rats. Co-administration of clozapine (1, 3 and 10 mg/kg s.c.) dos e-dependently inhibited loxapine-induced catalepsy. Clozapine (10 mg/k g s.c.) also prevented the induction of catalepsy by olanzapine. In ad dition, clozapine abolished the catalepsy induced by loxapine when it was administered after the response had fully developed. In contrast, the duration of SCH 23390-induced catalepsy was prolonged by clozapine , indicating that its anti-catalepsy effects against olanzapine and lo xapine are unlikely to be caused by muscle relaxation, sedation or sti mulation. Since SCH 23390-induced catalepsy is reported to be blocked by scopolamine, dizocilpine (MK-801) or 8-hydroxy-dipropylamino-tetral in, it is unlikely that muscarinic blockade, NMDA ion channel blockade and 5-HT1A receptor agonism, respectively, are involved in clozapine' s action, but the mechanism by which clozapine exerts this anti-catale ptic effect remains unknown.