Inhibition of Epinephrine-Induced Hyperglycemia With Adrenergic Blocking Drugs

Abstract

Adrenergic blocking drugs were injd. intraven. into unanesthetized rabbits to test their effects on hyperglycemia induced by an intraven. injn. of a physiological dose of epinephrine (4 ug./kg.). With the exception of dihydroergocornine, all compounds were aryl-substituted 2-haloalkylamines. The effectiveness of these compounds is probably related to their potency as measured by antagonism of other effects of epinephrine, because the most potent drugs blocked or diminished hyperglycemia in a dose of 2 mg./kg., whereas less potent homologs required a dose of 5 mg./kg. The least potent compounds did not reduce the hyperglycemia even in a dose of 10 mg./kg. When the halogen of an alkylamine was replaced by an hydroxyl radical, the resulting agent lost its adrenergic blocking activity and its ability to block epinephrine hyperglycemia. These data and other evidence indicates that a characteristic property of the more potent adrenergic blocking drugs is the ability to diminish epinephrine hyperglycemia.