Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan.
Eur J Pharmacol. 2012 Mar 15;679(1-3):127-31. doi: 10.1016/j.ejphar.2012.01.019. Epub 2012 Feb 1.
α(1)-Adrenoceptor antagonists are widely used for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Activation of α(1)-adrenoceptors is reported to induce salivary secretion in rats and humans. However, the effects of α(1)-adrenoceptor antagonists on salivary secretion remain unknown. Here, we investigated the effects of the α(1)-adrenoceptor antagonists prazosin, silodosin, tamsulosin and urapidil on phenylephrine-induced salivary secretion and compared the results with the effects on phenylephrine-induced intraurethral pressure (IUP) elevation in anesthetized rats. All antagonists inhibited phenylephrine-induced salivary secretion and IUP elevation in a dose-dependent fashion. Comparison of DR(10) values (the dose required to shift the dose-response curve 10-fold to the right) in both tissues showed that the inhibitory effect of silodosin was significantly more potent in the salivary gland than in the urethra (18-fold), but tamsulosin (2.3-fold), prazosin (1.7-fold) and urapidil (1.1-fold) did not show comparable tissue selectivity. These results suggest that α(1)-adrenoceptor antagonists inhibit not only urethral contraction but also salivary secretion, and that high tissue selectivity for the salivary gland over the urethra as shown by silodosin may contribute to the incidence of dry mouth.
α(1)-肾上腺素受体拮抗剂被广泛用于治疗与良性前列腺增生相关的排尿功能障碍。据报道，α(1)-肾上腺素受体的激活会引起大鼠和人类的唾液分泌。然而，α(1)-肾上腺素受体拮抗剂对唾液分泌的影响尚不清楚。在这里，我们研究了 α(1)-肾上腺素受体拮抗剂哌唑嗪、西洛多辛、坦索罗辛和优瑞比林对苯肾上腺素诱导的唾液分泌的影响，并将结果与它们对麻醉大鼠苯肾上腺素诱导的尿道内压（IUP）升高的影响进行了比较。所有的拮抗剂都以剂量依赖性的方式抑制苯肾上腺素诱导的唾液分泌和 IUP 升高。在两种组织中比较 DR(10)值（使剂量反应曲线向右移动 10 倍所需的剂量）表明，西洛多辛在唾液腺中的抑制作用明显强于尿道（18 倍），但坦索罗辛（2.3 倍）、哌唑嗪（1.7 倍）和优瑞比林（1.1 倍）没有表现出类似的组织选择性。这些结果表明，α(1)-肾上腺素受体拮抗剂不仅抑制尿道收缩，还抑制唾液分泌，西洛多辛对唾液腺的高组织选择性可能导致口干的发生率增加。
