Saw palmetto extracts potently and noncompetitively inhibit human alpha(1)-adrenoceptors in vitro

BACKGROUND. We wanted to test whether phytotherapeutic agents used in the t reatment of lower urinary tract symptoms have alpha(1)-adrenoceptor antagon istic properties in vitro. METHODS. Preparations of beta-sitosterol and extracts of stinging nettle, m edicinal pumpkin, and saw palmetto were obtained from several pharmaceutica l companies. They were tested for their ability to inhibit [H-3]tamsulosin binding to human prostatic alpha(1)-adrenoceptors and [ H-3]prazosin bindin g to cloned human alpha(1A)- and alpha(1B)-adrenoceptors. Inhibition of phe nylephrine-stimulated [H-3]inositol phosphate formation by cloned receptors was also investigated. RESULTS. Up to the highest concentration which could be tested, preparation s of beta-sitosterol, stinging nettle, and medicinal pumpkin were without c onsistent inhibitory effect in all assays. In contrast, all tested saw palm etto extracts inhibited radioligand, binding to human alpha(1)-adrenoceptor s and agonist-induced [H-3]inositol phosphate formation. Saturation binding experiments in the presence of a single saw palmetto extract concentration indicated a noncompetitive antagonism. The relationship between active con centrations in vitro and recommended therapeutic doses for the saw palmetto extracts was slightly lower than that for several chemically defined alpha (1)-adrenoceptor antagonists. CONCLUSIONS. Saw palmetto extracts have alpha(1)-adrenoceptor-inhibitory pr operties. Lf bioavailability and other pharmacokinetic properties of these ingredients are similar to those of the chemically defined alpha(1)-adrenoc eptor antagonists,alpha(1)-adrenoceptor antagonism might be involved in the therapeutic effects of these extracts in patients with lower urinary tract symptoms suggestive of benign prostatic obstruction. Prostate 38:208-215, 1999. (C) 1999 WiIey-Liss, Inc.