ALFUZOSIN, A SELECTIVE ALPHA-1-ADRENOCEPTOR ANTAGONIST IN THE LOWER URINARY-TRACT

1 Phenylephrine-induced contractions of rabbit isolated trigone and ur ethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2 The characteristics of [H-3]-p razosin binding to human prostatic adenoma tissue were evaluated. [H-3 ]-prazosin was potently displaced by alpha1-adrenoceptor specific agen ts including alfuzosin, its (+)- and (-)-enantiomers and prazosin (IC5 0 0.035, 0.023, 0.019 and 0.004 mum, respectively), but only weakly by alpha2-adrenoceptor selective agents, for example, yohimbine (IC50= 6 .0 muM).3 In the pithed rat, alfuzosin (0.03-0.3 mg kg-1, i.v.) marked ly inhibited pressor responses produced by the alpha1-selective agonis t, cirazoline but inhibited only slightly responses to the alpha2-sele ctive agonist, UK 14,304. Alfuzosin (I mg kg-1, i.v.) had minimal effe cts against responses mediated by stimulation of prejunctional alpha2- receptors (UK 14,304-induced inhibition of sympathetic tachycardia). 4 In the anaesthetized cat, alfuzosin (0.001-1 mg kg-1, i.v.) and prazo sin (0.001-0.3 mg kg-1, i.v.) produced dose-related inhibition of the increases in urethral pressure caused by stimulation of sympathetic hy pogastric nerves. Prazosin was approximately 5 fold more potent than a lfuzosin. When phenylephrine was employed to induce urethral and vascu lar alpha1-mediated tone simultaneously, prazosin inhibited both stimu li with similar potency whereas alfusozin was 3-5 fold more potent aga inst elevated urethral pressure. This functional uroselectivity of alf uzosin was more evident by the intraduodenal route, since doses of 0.0 3 and 0.1 mg kg-1 alfuzosin inhibited urethral pressure with minimal e ffects on arterial blood pressure. 5 Alfuzosin is a potent selective a lpha1-adrenoceptor antagonist in tissues of the lower urinary tract in cluding the human prostate. This provides a pharmacological basis for its use in the treatment of benign prostatic hypertrophy.