The effect of trycyclic antidepressants on 3H-dopamine uptake into synaptosomes obtained from rat striatum and mesolimbic cortical areas was examined. Chlorimipramine was found to be the most potent uptake inhibitor (IC50 of 3.2-3.8 X 10(-6) M) in both brain regions. Desmethylimipramine, protryptyline and iprindole were approximately one-half as potent (IC50 of 5.9-8.5 X 10(-6) M) in both brain areas. Kinetic constants obtained from Line-weaver-Burk plots in both areas revealed no alteration in Km for transport and a decrease in V max thus indicating a non-competitive inhibition. The effect of chlorimipramine on the release of 3H-dopamine from striatal synaptosomes required a concentration 10(-5) M for 50% release in 5 min. It is suggested that dopamine uptake inhibition may play some role in the action of tricyclic drugs, e.g., activation of schizophrenic psychopathology but that this action can not be solely responsible for their antidepressant properties.
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