Characteristics of α1-adrenoceptor antagonists-induced ejaculatory dysfunction on spontaneous seminal emission in rats

Abstract

Although α₁-adrenoceptor (α₁-AR) antagonists used to treat benign prostatic hyperplasia can cause ejaculation disorders, the aetiology of this adverse event is still controversial. Therefore, we investigated the effects of antagonists with different affinities for α₁-AR subtypes on ejaculatory function and their mechanisms of action in normal rats. In the spontaneous seminal emission (SSE) test, systemically administered prazosin, terazosin, tamsulosin and naftopidil decreased the weight of ejaculated seminal material in a dose-dependent manner; the potency order was as follows: tamsulosin > terazosin > prazosin > naftopidil. The selective α_1D-AR antagonist BMY7378 had no effect on SSE. Intrathecal tamsulosin and naftopidil did not inhibit SSE. Tamsulosin, the most potent, was ineffective as a single dose and significantly increased seminal vesicle fluid in rats treated for 2 weeks but did not significantly change retrograde ejaculation. These results indicated that the difference in inhibitory potency of the five α₁-AR antagonists against SSE was due to the involvement of α_1A-AR subtypes. Our results further suggested that α₁-AR antagonist-induced ejaculatory dysfunction at the peripheral level was mainly due to the loss of seminal emission, although some retrograde ejaculation may also be involved.