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The β-adrenoceptor antagonist, penbutolol, is an effective serotonin(1A) (5-HT(1A)) receptor antagonist in the rat and through this action enhances the ability of selective serotonin re-uptake inhibitors (SSRIs) to increase levels of serotonin in terminal fields. In healthy volunteers, penbutolol (40 mg orally), produced a modest attenuation of the prolactin response to the 5-HT(1A) receptor antagonist, buspirone (30 mg orally), but did not antagonise the hypothermic response. Furthermore, penbutolol addition (40 mg daily for 3 weeks) failed to improve the antidepressants. These preliminary data suggest that at the typical dose used to treat hypertension, penbutolol does not antagonise 5-HT(1A) autoreceptors in humans and does not augment the effect of serotonergic antidepressants in treatment non-responders.

Original publication




Journal article


Human Psychopharmacology

Publication Date





273 - 277