Effects of four different α1-adrenoceptor antagonists on α-adrenoceptor agonist-induced contractions in isolated mouse and hamster ureters

Purpose: To compare the efficacy of the selective α1A-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against α-adrenoceptor agonist-induced contractions in mouse and hamster ureters. Methods: The four α1-adrenoceptor antagonists were evaluated against norepinephrine-induced phasic contractions in mouse isolated ureteral preparations and against phenylephrine-induced sustained contractions in hamster isolated ureteral preparations using a functional experimental technique. Results: In mouse ureters, silodosin (a selective α1A-adrenoceptor antagonist), doxazosin (a nonselective α1-adrenoceptor antagonist), terazosin (a nonselective α1-adrenoceptor antagonist), and alfuzosin (a nonselective α1-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pKB value) was silodosin (9.47 ± 0.16) > doxazosin (8.62 ± 0.15) > terazosin (8.39 ± 0.16) > alfuzosin (8.03 ± 0.12). In hamster ureters, all four antagonists shifted the phenylephrine concentration-response curve to the right, the rank order of potencies being silodosin (10.09 ± 0.13) > doxazosin (8.22 ± 0.16) > terazosin (7.75 ± 0.15) > alfuzosin (7.70 ± 0.10). In each case, silodosin was much more potent than the other three drugs. Conclusion: In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this α1A-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.