ON THE MECHANISM OF ACTION OF CLOZAPINE ON THE ADRENERGIC NEURONE

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Abstract
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 α-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.