Clozapine inhibits catalepsy induced by olanzapine and loxapine, but prolongs catalepsy induced by SCH 23390 in rats |
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Authors: | H O Kalkman V Neumann M D Tricklebank |
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Institution: | (1) Preclinical Research Sandoz Pharma Ltd, Building 360-405, CH-4002 Basel, Switzerland, CH |
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Abstract: | Loxapine (0.3mg/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;
1mg/kg, s.c.), but not clozapine (10mg/kg, s.c.), induced catalepsy in rats. Co-administration of clozapine (1, 3 and 10mg/
kg s.c.) dose-dependently inhibited loxapine-induced catalepsy. Clozapine (10mg/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.
Received: 8 August 1996 / Accepted: 10 December 1996 |
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Keywords: | Clozapine Olanzapine Loxapine SCH 23390 Catalepsy |
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