Effects of tranylcypromine enantiomers on monoamine uptake and release and imipramine binding

Studies were carried out in vitro to determine effects of tranylcypromine enantiomers ([+]- and [-]-TCP) on uptake and release of 5-HT, DA and NA in rat synaptosomes and on imipramine binding to rabbit platelets. (+)-TCP was more potent than (-)-TCP as inhibitor of 5-HT uptake and imipramine binding, whereas (-)-TCP was more potent than (+)-TCP as inhibitor of DA and NA uptake. The enantiomers differed only slightly in their effects on monoamine release. The findings agree with previous reports on the stereo-selectivity of monoaminergic mechanisms toward TCP enantiomers, and support the notion that the 5-HT uptake site may be associated with the imipramine binding site.