Comparison of the Effects of Four α1 -Adrenoceptor Antagonists on Ejaculatory Function in Rats

• Published in: Urology (Ridgewood, N.J.) N.J.), 2012-08, Vol.80 (2), p.486.e9-486.e16
• Main Authors: Tatemichi, Satoshi, Kobayashi, Kumi, Yokoi, Ryohei, Kobayashi, Kazuo, Maruyama, Kazuyasu, Hoyano, Yuji, Kobayashi, Mamoru, Kuroda, Junji, Kusama, Hiroshi
• Format: Article
• Language: English
• Subjects: Adrenergic alpha-1 Receptor Antagonists - pharmacology; Animals; Ejaculation - drug effects; Ejaculation - physiology; Indoles - pharmacology; Male; Naphthalenes - pharmacology; Piperazines - pharmacology; Quinazolines - pharmacology; Rats; Rats, Sprague-Dawley; Sulfonamides - pharmacology; Urology
• ISSN: 0090-4295; 1527-9995
• DOI: 10.1016/j.urology.2012.01.039

Objective To compare the effects of four α1 -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 α1A -AR subtype—would be related to the prevalence of ejaculation disorder (EjD). Methods The effects of α1 -AR antagonists on noradrenaline-induced contractions were studied in rat isolated seminal vesicles, vas deferens, bladder trigone, and prostate. Male rats were given α1 -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 α1 -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 α1 -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 α1A -AR. Conclusion α1 -AR antagonists cause EjD as a class effect that depends on affinity for α1A -AR. Differences in α1A -AR selectivity would be unlikely to be related to the incidence of EjD.