Alfuzosin, a selective α 1 ‐adrenoceptor antagonist in the lower urinary tract

1 Phenylephrine‐induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA 2 7.44 and 7.30, respectively) and prazosin. 2 The characteristics of [ 3 H]‐prazosin binding to human prostatic adenoma tissue were evaluated. [ 3 H]‐prazosin was potently displaced by α 1 ‐adrenoceptor specific agents including alfuzosin, its (+)‐ and (−)‐enantiomers and prazosin (IC 50 0.035, 0.023, 0.019 and 0.004 μ m , respectively), but only weakly by α 2 ‐adrenoceptor selective agents, for example, yohimbine (IC 50 = 6.0 μ m ). 3 In the pithed rat, alfuzosin (0.03–0.3 mg kg − 1, i.v.) markedly inhibited pressor responses produced by the α 1 ‐selective agonist, cirazoline but inhibited only slightly responses to the α 2 ‐selective agonist, UK 14,304. Alfuzosin (1 mg kg −1 , i.v.) had minimal effects against responses mediated by stimulation of prejunctional α 2 ‐receptors (UK 14,304‐induced inhibition of sympathetic tachycardia). 4 In the anaesthetized cat, alfuzosin (0.001–1 mg kg −1 , i.v.) and prazosin (0.001–0.3 mg kg −1 , i.v.) produced dose‐related inhibition of the increases in urethral pressure caused by stimulation of sympathetic hypogastric nerves. Prazosin was approximately 5 fold more potent than alfuzosin. When phenylephrine was employed to induce urethral and vascular α 1 ‐mediated tone simultaneously, prazosin inhibited both stimuli with similar potency whereas alfusozin was 3–5 fold more potent against elevated urethral pressure. This functional uroselectivity of alfuzosin was more evident by the intraduodenal route, since doses of 0.03 and 0.1 mg kg −1 alfuzosin inhibited urethral pressure with minimal effects on arterial blood pressure. 5 Alfuzosin is a potent selective α 1 ‐adrenoceptor antagonist in tissues of the lower urinary tract including the human prostate. This provides a pharmacological basis for its use in the treatment of benign prostatic hypertrophy.