Comparison of the effects of four α1-adrenoceptor antagonists on ejaculatory function in rats.
OBJECTIVE
To compare the effects of four α(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 α(1A)-AR subtype-would be related to the prevalence of ejaculation disorder (EjD).


METHODS
The effects of α(1)-AR antagonists on noradrenaline-induced contractions were studied in rat isolated seminal vesicles, vas deferens, bladder trigone, and prostate. Male rats were given α(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 α(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 α(1)-AR antagonists dose-dependently decreased NP and inhibited the phenylephrine-induced increase in IUP. There was little difference in the dose ratio ID(50) value (dose required to produce 50% inhibition) for NP/ID(50) value for IUP response among the four drugs. Drug potencies associated NP and IUP correlated closely with affinities for the human α(1A)-AR.


CONCLUSIONS
α(1)-AR antagonists cause EjD as a class effect that depends on affinity for α(1A)-AR. Differences in α(1A)-AR selectivity would be unlikely to be related to the incidence of EjD.
Development Research, R&D, Kissei Pharmaceutical, Co., Ltd., Nagano, Japan. satoshi_tatemichi@pharm.kissei.co.jp
Satoshi
S
Tatemichi
Kumi
K
Kobayashi
Ryohei
R
Yokoi
Kazuo
K
Kobayashi
Kazuyasu
K
Maruyama
Yuji
Y
Hoyano
Mamoru
M
Kobayashi
Junji
J
Kuroda
Hiroshi
H
Kusama
D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D004542:Ejaculation / Q000187:drug effects* / Q000502:physiology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011799:Quinazolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000494:pharmacology; D000077409:Tamsulosin
D058668:Adrenergic alpha-1 Receptor Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; D011799:Quinazolines; D013449:Sulfonamides; C047638:alfuzosin; C095285:silodosin; D000077409:Tamsulosin; C064357:naftopidil