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 i.v. sulpiride. This effect persisted after neuronal uptake blockade with desipramine, but was prevented by .alpha.2-adrenoceptor blockade with yohimbine. Positive chronotropic effects of i.v. norepinephrine were unchanged by sulpiride, suggesting that sympathetic nerve function was facilitated by 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. While sulpiride did not antagonize the pressor effect of the .alpha.1-adrenoceptor agonist phenylephrine, it significantly attenuated the increases in blood pressure produced by tramazoline. The .alpha.2-adrenoceptor blocking action of sulpiride lasted for .apprx. 15 min at 1.0 mg/kg and for 90 min at 2.0 mg/kg. 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. Peripheral neuronal and vascular dopamine receptors may be antagonized by sulpiride without affecting .alpha.-adrenergic mechanisms. At doses of 1.0 mg/kg and higher, sulpiride facilitates sympathetic nerve function by a preferential antagonism of .alpha.2-adrenoceptors.