Abstract

Isolated rabbit hearts were perfused with 20, 200 or 2000 ng/ml of either l-or d-norepinephrine, and the concentration in the effluent was determined fluorimetrically. With 20 ng/ml, equal amounts of l-or d-norepinephrine were removed by the heart from the perfusion fluid. Cocaine equally antagonized the uptake of either isomer. For both isomers saturation of uptake occurred with higher concentrations of norepinephrine. Isolated left atrial strips were driven at a constant rate, and dose-response curves were determined for the positive inotropic effects of the isomers. Cocaine (7.5 µg/ml) increased the sensitivity to l-norepinephrine but not to the d-isomer. In concentrations of more than 300 ng/ml d-norepinephrine potentiated the effects of the l-isomer. The results indicate that the uptake of norepinephrine through the neuronal membrane has little or no stereospecificity. Hence, the stereospecificity of the sensitizing effect of cocaine can no longer be ascribed to differences in the rate of uptake of the isomers. It is proposed that lack of potentiation of d-norepinephrine by cocaine is due to the low potency of this isomer which exerts pharmacological effects only in concentrations which saturate the uptake mechanism; the effect of cocaine becomes negligible when uptake is saturated.