Hyperforin, a Major Antidepressant Constituent of St. John's Wort, Inhibits Serotonin Uptake by Elevating Free Intracellular Na ϩ1 1

ABSTRACT Extracts of Hypericum perforatum (St. John's Wort) are widely used for the treatment of depressive disorders and are unspecific inhibitors of the neuronal uptake of several neurotransmitters. Previous studies have shown that hyperforin represents the reuptake inhibiting constituent. To characterize the mechanism of serotonin reuptake inhibition, kinetic analyses in synaptosomes of mouse brain were performed. Michaelis-Menten kinetics revealed that hyperforin (2 M) induces a decrease in V max by more than 50% while only slightly decreasing K m , indicating mainly noncompetitive inhibition. By contrast, citalopra