Comparison of the effects of four α1-adrenoceptor antagonists on ejaculatory function in rats.

OBJECTIVE To compare the effects of four alpha(1)-adrenoceptor (AR) subtype-selective antagonists on ejaculatory function in rats to investigate whether the differences in their modes of action-based on their selectivities for the alpha(1A)-AR subtype-would be related to the prevalence of ejaculation disorder (EjD). METHODS The effects of alpha(1)-AR antagonists on noradrenaline-induced contractions were studied in rat isolated seminal vesicles, vas deferens, bladder trigone, and prostate. Male rats were given alpha(1)-AR antagonists orally and, 1 hour after the drug administration they were cohoused in pairs for 1 hour with untreated female rats certified to be in estrus. The number of copulatory plugs (NP) present after mating was measured as a marker of EjD. Drug effects on ejaculatory function (ie, on NP) were compared with those on the prostatic urethra (ie, phenylephrine-induced increase in intraurethral pressure [IUP]). RESULTS All alpha(1)-AR antagonists concentration-dependently inhibited noradrenaline-induced contraction in all 4 tissues, and there were no differences in the rank order of potencies (tamsulosin > silodosin > alfuzosin > naftopidil) among the tissues. All alpha(1)-AR antagonists dose-dependently decreased NP and inhibited the phenylephrine-induced increase in IUP. There was little difference in the dose ratio ID50 value (dose required to produce 50% inhibition) for NP/ID50 value for IUP response among the four drugs. Drug potencies associated NP and IUP correlated closely with affinities for the human alpha(1A)-AR. CONCLUSION alpha(1)-AR antagonists cause EjD as a class effect that depends on affinity for alpha(1A)-AR. Differences in alpha(1A)-AR selectivity would be unlikely to be related to the incidence of EjD. UROLOGY 80: 486.e9-486.e16, 2012. (c) 2012 Elsevier Inc.