Kobayashi Shinya, Tomiyama Yoshitaka, Maruyama Kazuyasu, Hoyano Yuji, Yamazaki Yoshinobu, Kusama Hiroshi
Pharmacology, Research and Development, Kissei Pharmaceutical Co. Ltd., Azumino, Nagano, Japan.
J Smooth Muscle Res. 2009 Aug;45(4):187-95. doi: 10.1540/jsmr.45.187.
To compare the efficacy of the selective alpha(1A)-adrenoceptor antagonist silodosin with those of doxazosin, terazosin, and alfuzosin against alpha-adrenoceptor agonist-induced contractions in mouse and hamster ureters.
The four alpha(1)-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.
In mouse ureters, silodosin (a selective alpha(1A)-adrenoceptor antagonist), doxazosin (a nonselective alpha(1)-adrenoceptor antagonist), terazosin (a nonselective alpha(1)-adrenoceptor antagonist), and alfuzosin (a nonselective alpha(1)-adrenoceptor antagonist) all shifted the norepinephrine concentration-response curve to the right. The rank order of potencies (pK(B) 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.
In this study, silodosin suppressed both mouse and hamster ureteral contractions more potently than doxazosin, terazosin, or alfuzosin. Hence, this alpha(1A)-adrenoceptor antagonist warrants further study as a potentially very useful medication for stone passage in urolithiasis patients.
比较选择性α(1A)-肾上腺素能受体拮抗剂西洛多辛与多沙唑嗪、特拉唑嗪和阿夫唑嗪对小鼠和仓鼠输尿管中α-肾上腺素能受体激动剂诱导的收缩作用的疗效。
采用功能实验技术，评估这四种α(1)-肾上腺素能受体拮抗剂对小鼠离体输尿管制剂中去甲肾上腺素诱导的相性收缩以及对仓鼠离体输尿管制剂中苯肾上腺素诱导的持续性收缩的作用。
在小鼠输尿管中，西洛多辛（一种选择性α(1A)-肾上腺素能受体拮抗剂）、多沙唑嗪（一种非选择性α(1)-肾上腺素能受体拮抗剂）、特拉唑嗪（一种非选择性α(1)-肾上腺素能受体拮抗剂）和阿夫唑嗪（一种非选择性α(1)-肾上腺素能受体拮抗剂）均使去甲肾上腺素浓度-反应曲线右移。效价顺序（pK(B)值）为西洛多辛（9.47±0.16）>多沙唑嗪（8.62±0.15）>特拉唑嗪（8.39±0.16）>阿夫唑嗪（8.03±0.12）。在仓鼠输尿管中，所有四种拮抗剂均使苯肾上腺素浓度-反应曲线右移，效价顺序为西洛多辛（10.09±0.13）>多沙唑嗪（8.22±0.16）>特拉唑嗪（7.75±0.15）>阿夫唑嗪（7.70±0.10）。在每种情况下，西洛多辛的效力均远高于其他三种药物。
在本研究中，西洛多辛抑制小鼠和仓鼠输尿管收缩的效力比多沙唑嗪、特拉唑嗪或阿夫唑嗪更强。因此，这种α(1A)-肾上腺素能受体拮抗剂作为一种对尿路结石患者排石可能非常有用的药物，值得进一步研究。
