THE INFLUENCE OF COCAINE ON SOME METABOLIC EFFECTS AND THE DISTRIBUTION OF CATECHOLAMINES

¹ Department of Pharmacology, Division of Basic Health Sciences, Emory University, Atlanta, Georgia

The influence of cocaine on the effects of epinephrine and norepinephrine on plasma glucose, lactate, and free fatty acids (FFA) and on the distribution of injected epinephrine-H³ and norepinephrine-H³ in plasma, fat, and liver was studied in anesthetized dogs.

Plasma glucose, lactate, and FFA responses to 1, 3, and 10 µg/kg of norepinephrine given intravenously were greater when cocaine (10 mg/kg) was given 15 minutes earlier. These responses to epinephrine were potentiated by cocaine to a much smaller degree, if at all.

Cocaine delayed the removal of injected epinephrine and norepinephrine from the plasma during the first 5 minutes after injection of the amines. However, this factor could not completely account for the potentiation of the pressor effect of norepinephrine seen in these experiments. Cocaine impaired the ability of fat and liver to bind both epinephrine-H³ and norepinephrine-H³ as early as 2 minutes after injection of the amines. Tissue binding in the absence of cocaine was much greater for norepinephrine than for epinephrine. The potentiation by cocaine of the effects of norepinephrine on fat and liver which result in increases in plasma levels of FFA and glucose, thus is accompanied by an inhibition of the binding of the amine in these tissues. While cocaine has a similar effect on the tissue binding of epinephrine, little or no potentiation occurs presumably because this binding is not as great a factor in the inactivation of injected epinephrine as it is in the case of norepinephrine.