THE EFFECT OF BRETYLIUM ON AMINE RETENTION IN RAT HEART

¹ Laboratory of Clinical Science, National Institute of Mental Health, Bethesda, Maryland

Bretylium, a compound which blocks release of norepinephrine from sympathetic nerve endings, has been found to deplete myocardial stores of metaraminol and several other "false" transmitters but does not alter levels of cardiac norepinephrine or -methylnorepinephrine. Bretylium is more effective than desmethylimipramine or cocaine in reducing metaraminol levels although these drugs more effectively inhibit uptake of metaraminol. Since bretylium does not appear to displace amines at their binding sites nor accelerate metabolism of metaraminol, these results suggest that a drug-membrane interaction other than inhibition of uptake is the basis for the release of these amines. The susceptibility to release appears to be inversely related to the affinity of the amines to binding sites within the neuron, and it is suggested that bretylium acts directly or indirectly to alter the rate of efflux of these amines from the neuronal cytoplasm.