In vivo actions of clozapine and haloperidol on the turnover rate of acetylcholine in rat striatum.
We have measured acetylcholine (ACh) content and turnover rate (TRACh) in striatum and cortex of rats receiving haloperidol and clozapine i.p. Both clozapine (30 mumol/kg) and haloperidol (10 mumol/kg) reverse the decrease in striatal TRACh elicited by apomorphine (11 mumol/kg) while each antipsychotic affects the steady state and the TRACh in striatum differently. Haloperidol fails to change striatal ACh content but increases the TRACh; chozapine (15 and 30 mumol/kg) neither decreases the content of ACh nor changes the TRACh in striatum. Moreover, 60 or 90 mumol/kg of clozapine causes a 40% decrease in ACh content without affecting the TRACh. Clozapine, but not haloperidol, antagonizes the increase in ACh content and the decrease in TRACh elicited by arecoline (64 mumol/kg) and oxotremorine (9 mumol/kg) in striatum. Clozapine resembles trihexylphenidyl (14 mumol/kg) and benztropine (12 mumol/kg) because it decreases the ACh content of striatum without changing the TRACh. Moreover, clozapine and benztropine reverse the increase in striatal TRACh elicited by haloperidol. The increase in striatal TRACh elicited by haloperidol could be of value to explain the extrapyramidal action of this drug. The anticholinergic action of clozapine could explain the absence of extrapyramidal side effects observed with this drug.
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001590:Benztropine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D003984:Dibenzazepines / Q000494:pharmacology*; D004298:Dopamine / Q000502:physiology; D004347:Drug Interactions; D006801:Humans; D007700:Kinetics; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010095:Oxotremorine / Q000494:pharmacology; D051381:Rats; D011955:Receptors, Drug / Q000187:drug effects; D013239:Stereotyped Behavior / Q000187:drug effects; D014282:Trihexyphenidyl / Q000494:pharmacology
D003984:Dibenzazepines; D011955:Receptors, Drug; D001590:Benztropine; D010095:Oxotremorine; D014282:Trihexyphenidyl; D003024:Clozapine; D001058:Apomorphine; D004298:Dopamine