Effects of tranylcypromine on 5-HT uptake and its interaction with PCPA on rat brain 5-HT.

The effect of p-chlorophenylalanine-treatment in rats receiving chronic treatment with tranylcypromine on brain serotonin and 5-hydroxyindoleacetic acid levels was examined. This treatment schedule was similar to that followed in depressed patients undergoing treatment with the monoamine oxidase inhibitor. PCPA completely obviated the elevation in serotonin and further reduced 5-HIAA levels of animals treated chronically with tranylcypromine. These effects correlated with PCPA-induced reversal in the clinical improvement achieved by tranylcypromine. In in vitro studies, tranylcypromine was found to inhibit 5-HT uptake into synaptosomes with a minimal action on the spontaneous release of the amine.