Michel M C
Department of Pharmacology & Pharmacotherapy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Br J Pharmacol. 2007 Oct;152(3):289-90. doi: 10.1038/sj.bjp.0707369. Epub 2007 Jul 2.
The abnormal ejaculation of semen is a typical but infrequent side effect of some alpha(1)-adrenoceptor antagonists, particularly those with selectivity for alpha(1A)-adrenoceptors such as silodosin or tamsulosin. Recent clinical studies suggest that this represents a relative anejaculation rather than a retrograde ejaculation. An elegant study in this issue of the journal using alpha(1A) single and alpha(1A/B/D) triple knock-out mice reports a similar phenomenon in rodents. Using a multi-disciplinary approach, the reduced ejaculation and related male infertility is shown to be caused by an impaired function of the vas deferens rather than by alterations in sperm formation, number or function. Similarities and differences between mouse and human data are discussed, particularly why a complete inhibition of all three alpha(1)-adrenoceptor subtypes has the strongest effects in mice whereas apparently only alpha(1A)-adrenoceptor-selective drugs impair ejaculatory function in humans.
精液异常射出是某些α(1)-肾上腺素能受体拮抗剂典型但不常见的副作用,尤其是那些对α(1A)-肾上腺素能受体具有选择性的药物,如西洛多辛或坦索罗辛。最近的临床研究表明,这表现为相对性无射精而非逆行射精。本期杂志上一项使用α(1A)单基因敲除和α(1A/B/D)三基因敲除小鼠的出色研究报告了啮齿动物中类似的现象。采用多学科方法研究发现,射精减少及相关男性不育是由输精管功能受损所致,而非精子生成、数量或功能改变引起。文中讨论了小鼠和人类数据的异同,特别是为何完全抑制所有三种α(1)-肾上腺素能受体亚型在小鼠中产生的影响最强,而在人类中显然只有α(1A)-肾上腺素能受体选择性药物会损害射精功能。