On the mechanism of action of clozapine on the adrenergic neurone.
1 The antipsychotic drug, clozapine, lowered noradrenaline and metaraminol (MA) concentrations in the rat heart. This action was blocked by the presence of a ganglionic blocking drug. 2 Other alpha-adrenoceptor blocking drugs (phenoxybenzamine, phentolamine) did not significantly lower heart amine concentrations. An inhibitor of neuronal amine uptake (desipramine) caused only a slight lowering. The combination of phentolamine and desipramine showed considerable activity, and this action was blocked by ganglionic blockade. 3 Clozapine had little or no action in blocking amine uptake, yet greatly potentiated amine release caused by the phentolamine-desipramine combination. 4 Other antipsychotic drugs (haloperidol, chlorpromazine, thioridazine) or other agents (propranolol, atropine) did not share this action of clozapine. 5 Ganglionic blockade markedly delayed amine release induced by reserpine administration. 6 It is suggested that clozapine may have an incomplete reserpine-like effect specifically on the adrenergic neurone, facilitating impulse-induced amine release.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002714:Chlorisondamine / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D005260:Female; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D008680:Metaraminol / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D051381:Rats; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D014150:Antipsychotic Agents; D003984:Dibenzazepines; D008680:Metaraminol; D003024:Clozapine; D002714:Chlorisondamine; D009638:Norepinephrine