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St. John's wort: New study may shed light on mechanism of antidepressant action

Extracts of St. John's wort (Hypericum perforatum) are used widely in Germany and the United States as antidepressant agents in cases of mild-to-moderate depression. Yet the mechanism of action remains unknown. Previous studies have pinpointed several weak effects, yet none seem sufficient to explain the extract's activity. There are at least ten potentially pharmacologically active components in the extract, one of which is hypericin, the substance believed to have the greatest degree of involvement in the extract's antidepressant effects. The present study examined the affinity of hypericin at 30 receptor or uptake sites; it inhibited less than 40% of specific radioligand binding at all sites except mAChR and alpha receptors. The alpha receptor finding is novel and is a potentially important clue to the mechanism of action of St. John's wort, as these receptors have been found to have an association with the antidepressant action of synthetic agents such as MAO inhibitors and selective 5-HT reuptake inhibitors (SSRI). Though the efficacy of St. John's wort as an antidepressant may be attributed to the concerted activity of several mechanisms, the affinity of hypericin for alpha receptors presents new possibilities for the cause of this extract's clinical success.

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Raffa R., "Screen of receptor and uptake-site activity of hypericin component of St. John's wort reveals alpha receptor binding." Life Sciences 1998; 62(16):PL 265-270.

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