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. 1993 Aug;109(4):1282–1289. doi: 10.1111/j.1476-5381.1993.tb13762.x

Alfuzosin, a selective alpha 1-adrenoceptor antagonist in the lower urinary tract.

F Lefèvre-Borg 1, S E O'Connor 1, H Schoemaker 1, P E Hicks 1, J Lechaire 1, E Gautier 1, F Pierre 1, C Pimoule 1, P Manoury 1, S Z Langer 1
PMCID: PMC2175718  PMID: 8104650

Abstract

1. Phenylephrine-induced contractions of rabbit isolated trigone and urethra were antagonized in a competitive manner by alfuzosin (pA2 7.44 and 7.30, respectively) and prazosin. 2. The characteristics of [3H]-prazosin binding to human prostatic adenoma tissue were evaluated. [3H]-prazosin was potently displaced by alpha 1-adrenoceptor specific agents including alfuzosin, its (+)- and (-)-enantiomers and prazosin (IC50 0.035, 0.023, 0.019 and 0.004 microM, respectively), but only weakly by alpha 2-adrenoceptor selective agents, for example, yohimbine (IC50 = 6.0 microM). 3. In the pithed rat, alfuzosin (0.03-0.3 mg kg-1, i.v.) markedly inhibited pressor responses produced by the alpha 1-selective agonist, cirazoline but inhibited only slightly responses to the alpha 2-selective agonist, UK 14,304. Alfuzosin (1 mg kg-1, i.v.) had minimal effects against responses mediated by stimulation of prejunctional alpha 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 alpha 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.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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