Contributions of alpha-adrenoreceptor blockade to extrapyramidal effects of neuroleptic drugs.

Prazosin, phenoxybenzamine and clozapine, but not sulpiride, abolished the increase in flexor reflex activity induced by clonidine and they accelerated the noradrenaline utilization in the brain of rats. These findings indicate that the first three drugs block central alpha-adrenoreceptors. The alpha-methyltyrosine-induced disappearance of dopamine in the corpus striatum and the limbic system was decelerated by prazosin and phenoxybenzamine, was accelerated by sulpiride and was not significantly changed by clozapine. Prazosin and phenoxybenzamine almost completely reversed the sulpiride-induced increase in dopamine utilization. The reduction of the dopamine release following blockade of postsynaptic alpha-adrenoreceptors might prevent tardive dyskinesia. Blockade of postsynaptic alpha-adrenoreceptors might also increase the ultimate result of dopamine receptor stimulation in the corpus striatum but decrease that in the limbic system. Therefore, blockade of alpha-adrenoreceptors as well as of muscarinic receptors might explain why clozapine causes less extrapyramidal disturbances than other antipsychotic drugs.