Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain

Abstract

Abstract The effect of dextromethorphan on the uptake and metabolism of 5-hydroxytryptamine (5-HT) was studied in human blood platelets and in rat brain. In the concentration of 120 nM dextromethorphan inhibited the uptake of 5-HT (1 μM) into platelets by 50%. The corresponding concentrations of imipramine and methadone under similar conditions were 22 and 590 nM, respectively. Dextromethorphan (20 to 40 mg kg−1) decreased the concentration of brain 5-hydroxyindoleacetic acid (5-HIAA) and the probenecid-induced accumulation of 5-HIAA time- and dose-dependently. However, dextromethorphan did not alter the pargyline-induced changes in brain 5-HT metabolism. Dextromethorphan-induced changes in brain 5-HT metabolism could arise from the inhibition of the reuptake of 5-HT into neurons.