THE EFFECT OF COCAINE AND OF PRETREATMENT WITH RESERPINE ON THE UPTAKE OF TYRAMINE-2-C¹⁴ AND dl-EPINEPHRINE-2-C¹⁴ INTO HEART AND SPLEEN

¹ Department of Pharmacology, Harvard Medical School, Boston, Massachusetts

The total radioactivity of blood, heart and spleen of the pithed rat was measured 2 minutes after the intravenous injection of either 20 µg/kg dl-epinephrine-2-C¹⁴ or 100 µg/kg tyramine-2-C¹⁴. After 20 mg/kg cocaine hydrochloride, the injection of epinephrine caused a higher level of radioactivity in plasma than in control preparations; this was associated with an increased pressor response. Pretreatment with a single dose of 3 mg/kg reserpine phosphate failed to cause supersensitivity to epinephrine: it also failed to cause an increased plasma level of radioactivity. Two minutes after the injection of epinephrine the radioactivity of the heart (cpm per g) was 3.7 times higher than that of the plasma (cpm per ml); this ratio was not affected by prior administration of cocaine or by pretreatment with reserpine.

The pressor response to tyramine was reduced by cocaine and by pretreatment with reserpine, the latter being the more effective procedure. There was a marked accumulation of radioactivity in the heart and spleen in control preparations as well as after cocaine and after pretreatment with reserpine.

The results indicate that neither cocaine nor pretreatment with reserpine blocks the immediate uptake of epinephrine and tyramine into the tissues. It is possible that effects of cocaine and of pretreatment with reserpine on much smaller storage sites may be completely masked by this early and temporary binding by the tissues of large amounts of the amines.