POTENTIATION BY 3,4-DIMETHOXYPHENYLETHYLAMINE (DMPEA) AND COCAINE OF NOREPINEPHRINE-INDUCED CONTRACTION OF GUINEA-PIG VAS DEFERENS

¹ Ensor Foundation Research Laboratory, William S. Hall Psychiatric Institute, Columbia, South Carolina and The Department of Pharmacology, Medical College, Baroda, India

The influence of 3,4-dimethoxyphenylethylamine (DMPEA) and of cocaine on the responses of isolated guinea-pig vas deferens to norepinephrine (NE), methoxamine, acetylcholine (ACh) and histamine was examined. Alone DMPEA (1.0 and 3.0 µg/ml) and cocaine (0.1, 0.3, 1.0 and 10.0 µg/ml) did not exert any effect on the vas deferens but shifted the dose-response curves for the contractile effect of NE to the left and also increased the maximal responses. The contractile responses to NE were potentiated by lower concentrations of cocaine than of DMPEA. DMPEA (3 µg/ml) and cocaine (10 µg/ml) were equally effective in producing leftward shift of the dose-response curve for the contractile effect of methoxamine. Both DMPEA and cocaine produced slight shifts of the ACh and histamine dose-response curves: the maximum responses to ACh were significantly increased whereas those to histamine were not affected. Denervation induced a greater shift of the NE dose-response curve than that induced by cocaine. Our data indicate that cocaine-induced supersensitivity has both pre-and postjunctional components is specific for NE and is due to interference with the neuronal uptake process; the second component is nonspecific since responses to NE as well as to ACh are increased. DMPEA-induced supersensitivity is almost entirely postjunctional.