Clozapine--a serotonin antagonist?
The effect of clozapine on the central serotonergic transmission system was studied by investigation of open-field motility of rats after microinjection of drugs into nucleus accumbens and median raphe nucleus. Previous work has shown that LSD in low doses potentiates apomorphine-induced hypermotility and that this LSD effect is induced by a serotonin agonist action in median raphe nucleus. Clozapine, injected into median raphe nucleus (0.05 micrograms), suppressed the LSD effect in the same manner as serotonin antagonists did. Since alpha-adrenergic drugs, injected into median raphe nucleus, caused locomotor stimulant effects, an alpha- adrenalytic action of clozapine was excluded. Clozapine, injected into nucleus accumbens (0.2 micrograms), increased apomorphine-induced hypermotility, whereas the dopamine antagonist haloperidol suppressed it. Our results suggest a serotonin antagonist action of clozapine.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003000:Clonidine / Q000008:administration & dosage; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000008:administration & dosage; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000187:drug effects; D010646:Phentolamine / Q000008:administration & dosage; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*
D003984:Dibenzazepines; D012702:Serotonin Antagonists; D008238:Lysergic Acid Diethylamide; D003024:Clozapine; D006220:Haloperidol; D003000:Clonidine; D001058:Apomorphine; D010646:Phentolamine