Evaluation of peripheral dopamine receptor and alpha-adrenoceptor blocking activity of sulpiride

The effect of sulpiride, a dopamine receptor antagonist, on peripheral alpha-adrenoceptors and dopamine receptors was determined. Positive chronotropic responses to cardioaccelerator nerve stimulation in pentobarbital-anesthetized dogs were potentiated by 1.0 and 2.0 mg/kg but not by 0.5 mg/kg intravenous sulpiride. This effect persisted after neuronal uptake blockade with desipramine, but was prevented by alpha 2-adrenoceptor blockade with yohimbine. Positive chronotropic effects of intravenous norepinephrine were unchanged by sulpiride, suggesting that sympathetic nerve function was facilitated via a presynaptic mechanism. Since yohimbine prevented the facilitatory action of sulpiride, an analysis of the ability of sulpiride to antagonize alpha-adrenoceptors was made. The reduction in stimulus-induced tachycardia caused by the alpha 2-adrenoceptor agonist tramazoline was significantly antagonized by sulpiride. Furthermore, while sulpiride did not antagonize the pressor effect of the alpha-adrenoceptor agonist phenylephrine, it significantly attenuated the increases in blood pressure produced by tramazoline. The alpha 2-adrenoceptor blocking action of sulpiride lasted for approximately 15 min at 1.0 mg/kg adn for 90 min at 2.0 mg/kg. In additional experiments, it was determined that the dopamine receptor-mediated bradycardic and hypotensive effects of N,N-di-n-propyldopamine were antagonized for at least 2 h by 0.1, 0.5, and 1.0 mg/kg sulpiride. These studies establish that peripheral neuronal and vascular dopamine receptors may be antagonized by sulpiride without affecting alpha-adrenergic mechanisms. However, at doses of 1.0 mg/kg and higher, sulpiride facilitates sympathetic nerve function via a preferential antagonism of alpha 2-adrenoceptors.