INHIBITION OF RENAL TUBULAR TRANSPORT OF CATECHOLAMINES BY COCAINE: AN ORGANIC BASE MECHANISM

¹ Pharmacology Department, State University of New York, Medical Center, Buffalo, New York

The effects of cocaine on the renal excretory transport of radioactively labeled norepinephrine, epinephrine, dopamine, tyramine, m-tyramine, 3,4-dimethoxyphenylethylamine, phenylethylamine and tetraethylammonium were studied in chickens by use of the Sperber technique. The transport of all of these organic cations except phenylethylamine was decreased significantly by cocaine. These data reinforce the earlier hypothesis that the catecholamines and other amines studied occupied the organic base (cation) transport system and reveal that cocaine is a competitor for organic cation transportbut not for organic anion transport. Cocaine failed to inhibit transport of label during phenylethylamine infusion because phenylethylamine is metabolized during transport by the renal tubule in the chicken and dog. About one-half of the infused phenylethylamine was recovered as an anionic metabolite and essentially no unmetabolized phenylethylamine was found in the urine. These data showing phenylethylamine metabolism to an anion in the kidney help to explain the mechanism by which probenecid inhibited phenylethylamine transport, as reported previously. Tricyclic antidepressants inhibited the renal tubular transport of norepinephrine.