The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation

Eur J Pharmacol. 2015 Jan 5;746:132-7. doi: 10.1016/j.ejphar.2014.11.006. Epub 2014 Nov 15.

Abstract

The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±μm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research.

Keywords: 4′O-methyl-quercetin (PubChem CID 5281699); Orthostatic hypotension; Pharmacodynamics; Quercetin; Quercetin (PubChem CID 5280343); Quercetin-3-glucuronide (PubChem CID 5274585); Supplement–drug interaction; Tamsulosin; Tamsulosin (PubChem CID 129211); Vasorelaxation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Supplements*
  • Drug Interactions
  • Hydrogen Peroxide / metabolism
  • Male
  • Phenylephrine / pharmacology
  • Quercetin / metabolism
  • Quercetin / pharmacology*
  • Rats
  • Rats, Wistar
  • Sulfonamides / pharmacology*
  • Tamsulosin
  • Vasodilation / drug effects*

Substances

  • Sulfonamides
  • Phenylephrine
  • Quercetin
  • Hydrogen Peroxide
  • Tamsulosin