COCAINE TACHYPHYLAXIS AND EFFECTS ON INDIRECTLY ACTING SYMPATHOMIMETIC DRUGS IN THE RABBIT AORTIC STRIP AND IN SPLENIC TISSUE

¹ Georgetown University, Medical and Dental Schools, Washington, D.C.

Tachyphylaxis was produced in spirally cut rabbit aortic strips by repeated applications of cocaine. Exposure of the preparation to norepinephrine restored the initial contraction heights. Aortic strips from reserpine-treated rabbits did not contract when exposed to indirectly-acting adrenergic drugs unless splenic slices of untreated rabbits were inserted in the organ bath. Cocaine produced tachyphylaxis and depressed the responses to other indirectly-acting adrenergic drugs, e.g., amphetamine and tyramine, in the biogenic source of catecholamine, using such depleted aortic strips as response indicators. Exhaustive washing and resting restored the reduced responses. When inhibitors of any step of the biosynthetic pathway of norepinephrine were incorporated into the bath fluid, the exhaustive washing and resting failed to restore the responses. Thus, resynthesis of essential norepinephrine in the biogenic source must have occurred during the rest period. Some monoamine oxidase inhibitors can be classified as indirectly-acting sympathomimetic drugs because their action mimicked that of l-amphetamine and cocaine.