BLOCKADE OF RESPONSES TO EPINEPHRINE AND NOREPINEPHRINE BY DIBENAMINE CONGENERS

¹ Department of Pharmacology, University of Michigan School of Medicine, Ann Arbor, Michigan
² Department of Pharmacology, University of Utah College of Medicine, Salt Lake City, Utah

The ability of -haloalkylamine adrenergic blocking agents to inhibit excitatory responses to epinephrine and norepinephrine has been studied in cats. The chronically denervated nictitating membrane and the intact vascular system during maximum stimulation of the vasodilator and cardiac stimulant responses by a continuous infusion of isopropylnorepinephrine have been employed as systems in which the recorded responses are almost entirely due to excitatory responses of smooth muscle.

These studies have revealed that responses to norepinephrine are blocked at least as readily and completely as responses to epinephrine. Data obtained from studies on the denervated nictitating membrane suggest that responses to norepinephrine may be blocked slightly more completely by a given dose of a -haloalkylamine than are responses to comparable doses of epinephrine. Pressor responses to small doses of epinephrine are "reversed" when only about 50 per cent of their vasoconstrictor action is eliminated.

These observations indicate that differences ill the net blood pressure response to various sympathomimetics after the administration of adrenergic blocking agents are largely due to differences in the magnitude of the vasodilator and cardiac stimulant components of their action, components which cannot be specifically inhibited by any of the currently known adrenergic blocking agents.