INFLUENCE OF COCAINE AND OF PRETREATMENT WITH RESERPINE ON THE PRESSOR EFFECT AND THE TISSUE UPTAKE OF INJECTED dl-CATECHOLAMINES-2-H³

¹ Institute of Pharmacology, University of Vienna, Vienna, Austria

The influence of cocaine or reserpine pretreatment on the blood pressure response to injected H³-dl-epinephrine or H³-dl-norepinephrine and on the uptake of these two catecholamines in tissues was studied in the pithed rat. Total radioactivity, H³-catecholamine level and also the concentration of the H³-O-methylated catecholamines were determined in the heart, spleen and plasma, 2 minutes after the injection of the labeled catecholamines. The blood pressure response to norepinephrine was more potentiated by cocaine than was that to an equivalent dose of epinephrine. Concomitantly cocaine also decreased the tissue level of both radioactivity and H3-catecholamine, more so for norepinephrine than for epinephrine. In the case of epinephrine, about 28% of the total radioactivity present in the hearts of the control rats must be attributed to metabolites. For norepinephrine this figure is about 21%. Cocaine significantly increased the degree of metabolism. It did not alter the total radioactivity level of the plasma.

Reserpine pretreatment also potentiated the blood pressure response towards H3-dl-norepinephrine and reduced the total radioactivity and the H³-norepinephrine concentration of the heart and spleen. Like cocaine, reserpine increased the relative amount of metabolites in the tissues. The total radioactivity and the concentration of H³-norepinephrine were reduced in the plasma of reserpine-pretreated animals. This finding may, at least in part, be explained by the increased plasma volume of these rats. It was concluded that, if determined 2 minutes after the injection of catecholamines, cocaine inhibits the uptake of these compounds into the tissues, thus producing supersensitivity. Reserpine, administered in 2 closes of 3 mg/kg, 42 and 18 hours prior to the actual experiment, also exerts similar actions, presumably by an entirely different mechanism.