Aminotetralin analogs of methoxamine as potential hypertensive agents

Cardiovascular effects of methoxamine and some aminotetralin derivatives (5,8-ADT, DR-31 and DR-17) were studied after systemic intravenous or intraarterial injection into different perfused vascular beds in anesthetized dogs. Intravenous administration of the compounds produced dose-related prolonged increases in blood pressure, which were antagonized by phentolamine. After intro-arterial injection into the perfused hindlimb, mesenteric artery or the saphenous vein, all compounds produced dose-dependent increases in perfusion pressure indicative of vasoconstriction. Phentolamine antagonized these effects. It was demonstrated that desipramine significantly reduced the vasoconstricting actions of intra-arterially injected tyramine in the hindlimb, but did not alter the responses induced by methoxamine and the aminotetralin derivatives. The data indicate that these compounds elicit peripheral vasoconstriction in the dog, through a direct action on the alpha adrenergic receptors.