AN ANALYSIS OF ADRENERGIC BLOCKING ACTIVITY

¹ Department of Pharmacology, Medical College of Georgia, Augusta, Georgia

We can now state that the production of ethylnorepinephrine "reversal" and the diminution but not reversal of the depressor response to isoproterenol are conclusive evidence of beta adrenergic blockade if the drug in question is not a peripheral vasoconstrictor or an alpha adrenergic blocking agent. Sixteen compounds have been studied to determine the presence or absence of adrenergic blocking activity and if present, the type of adrenergic blocking activity. The effects of pretreatment with these compounds on the mean arterial pressure, intestinal motility, heart rate and retractor penis muscle responses to epinephrine, phenylephrine, isoproterenol, and ethylnorepinephrine were determined in anesthetized, atropine-pretreated dogs.

Of the chloro and fluoro analogues of isoproterenol tested, those compounds possessing an alcoholic hydroxyl group exerted a beta adrenergic blocking action. Those analogues in which a chlorine atom was substituted for an alcoholic hydroxyl group were alpha adrenergic blocking agents.

The dextrorotatory isomer of isoproterenol was found to be devoid of any adrenergic blocking action.

Methoxyphenamine, dihydroergotamine and dihydroergocornine were found to be both alpha and beta adrenergic blocking agents. However, their alpha blocking activities were considerably more potent than their beta blocking activities.

The mechanism for isoproterenol "reversal" produced by pretreatment with phenylephrine or ergotamine we conclude to be a manifestation of cardiac stimulation by isoproterenol in the presence of a constricted peripheral vascular bed.