Mazindol, nomifensine and desmethylimipramine inhibit potassium-induced release of dopamine: effect of stimulus strength.

Abstract

Catecholamine uptake blockers exhibit a second action: They suppress the potassium (K+)-stimulated release of [3H]-dopamine (DA) from rat striatal tissue in vitro. In the present study, a K+ dose-response curve was obtained for the release of both [3H]-DA and endogenous DA from striatal tissue, in the absence and presence of catecholamine uptake blockers. Three drugs were used, namely, mazindol, nomifensine, and desmethylimipramine. The data showed that diminished release in the presence of mazindol or nomifensine was dependent upon the concentration of K+. Marked inhibition of stimulus-induced release of either 3H-DA or endogenous DA was observed at low concentrations of K+ (15 and 20 mM), but not at higher concentrations of K+ (40 and 60 mM). In contrast, the diminished release of DA in the presence of desmethylimipramine persisted over the K+ range of 20-60 mM. These data show that the drug action observed previously was not restricted to a specific neuronal pool of DA that was labelled with [3H]-DA. Further, the data emphasize the importance of the concentration of the depolarizing stimulus when evaluating the effects of drugs on release of catecholamines.