Mechanism of amphetamine accumulation in the isolated perfused heart of the rat

Abstract

Abstract Rat hearts were perfused with 10 to 1,000 ng/ml of (±)-[3H]amphetamine. The time course of accumulation and the maximal tissue/medium ratio (T/M) were identical for all concentrations studied. The maximal T/M varied between 5 and 6 and was reached after 5 min of perfusion. The accumulation of amphetamine was not inhibited by cocaine or noradrenaline. It was not impaired by combined inhibition of aerobic and anaerobic energy metabolism and it was not dependent on the intactness of sympathetic nerve endings, indicating that the greater amount of amphetamine was located extraneuronally. The diminished accumulation of amphetamine following reduction of temperature or sodium concentration of the perfusion fluid most probably reflects impaired tissue perfusion resulting from vascular constriction. The time course of accumulation and decay of amphetamine is compatible with a rapidly reversible phase-distribution of this amine possibly related to its relatively high lipophilic properties. The possible significance of phenolic hydroxyl groups in membrane transport and diffusion of phenethylamines is discussed.