Selective DA2 versus DA1 antagonist activity of domperidone in the periphery

Relative activity of domperidone as an antagonist of the two peripheral dopamine (DA) receptors, DA1 and DA2, was studied in pentobarbital-anesthetized dogs. Renal vasodilation produced by intra-arterial injection of DA into the phenoxybenzamine-pretreated renal vascular bed was the DA1-mediated response, while femoral vasodilation induced by dipropyl dopamine injected into the femoral artery with intact nerve supply was the DA2-mediated response. Domperidone, 0.5-5 micrograms/kg intravenously, inhibited the DA2 response by 15-75%. In contrast, doses up to 5 mg/kg had no effect on DA1-mediated or bradykinin-induced renal vasodilation. Domperidone has thus proved to be more selective than other DA2 antagonists, differentiating between the two peripheral DA receptors by a margin of greater than 10(4). Furthermore, domperidone was found to be selective as a DA2 versus alpha 2-adrenergic antagonist as studied on the dog cardioaccelerator nerve, thus, enhancing its value as a selective DA2 antagonist.