Effect of long term treatment with atypical neuroleptic drugs on beta adrenoceptor binding in rat cerebral cortex and myocardium.

Abstract

Several neuroleptic drugs enhance the release and the turnover of noradrenaline in the central nervous system and in peripheral organs. The present study demonstrates the effect of long term treatment (18 days) with atypical neuroleptic drugs (clozapine, thioridazine, and sulpiride) on beta-adrenoceptor density in the cerebral cortex and in the myocardium of rats. 1. Clozapine and thioridazine significantly reduced the number of 3H-dihydroalprenolol (DHA)-binding sites by 24 and 21%, respectively, in a crude cortical membrane fraction, and by 28 and 24% in myocardial membranes. 2. Sulpiride failed to alter the maximal number of binding sites in the cortex and in the myocardium. 3. The affinity of 3H-DHA to its binding sites remained unchanged by treatment with neuroleptic drugs. 4. Desipramine, which is known to reduce cerebral beta-adrenoceptors during chronic administration, was tested as reference compound. It proved to be more effective in this regard than clozapine and thioridazine in the cortex, but failed to reduce 3H-DHA binding in the myocardium. 5. Acute treatment with desipramine, clozapine, and thioridazine had no effect on 3H-DHA binding in the cerebral cortex. The decrease in beta-adrenoceptor density after long term treatment with neuroleptics may be ascribed to an increased concentration of noradrenaline at the receptor site due to antagonism at presynaptic alpha 2-adrenoceptors and inhibition of noradrenaline reuptake.