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.
D000317:Adrenergic alpha-Antagonists; D000818:Animals; D001060:Aporphines / Q000494:pharmacology; D004285:Dogs; D004558:Electric Stimulation; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D010868:Pimozide / Q000494:pharmacology; D011954:Receptors, Dopamine / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects
D000317:Adrenergic alpha-Antagonists; D001060:Aporphines; D011954:Receptors, Dopamine; D010868:Pimozide; D013469:Sulpiride; D006220:Haloperidol