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 catalepsy in rats. Co-administration of clozapine (1, 3 and 10 mg/kg s.c.) dose-dependently inhibited loxapine-induced catalepsy. Clozapine (10 mg/kg s.c.) also prevented the induction of catalepsy by olanzapine. In addition, 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 loxapine are unlikely to be caused by muscle relaxation, sedation or stimulation. Since SCH 23390-induced catalepsy is reported to be blocked by scopolamine, dizocilpine (MK-801) or 8-hydroxy-dipropylamino-tetralin, 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-cataleptic effect remains unknown.
Kalkman
H O
HO
Preclinical Research Sandoz Pharma Ltd., Basel, Switzerland.
Neumann
V
V
Tricklebank
M D
MD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001552:Benzazepines; D001569:Benzodiazepines; D002375:Catalepsy / Q000139:chemically induced / Q000517:prevention & control*; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008152:Loxapine; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives*; D051381:Rats; D017208:Rats, Wistar
D014150:Antipsychotic Agents; D001552:Benzazepines; D001569:Benzodiazepines; D010890:Pirenzepine; D003024:Clozapine; D008152:Loxapine; D000077152:Olanzapine