In vivo study on the effects of alpha1-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in male dogs.
Alpha-adrenoceptor antagonists are used worldwide for the treatment of voiding dysfunction associated with benign prostatic hyperplasia. Recently, abnormal ejaculation, an adverse effect associated with their use, has attracted attention. Here, we simultaneously investigated the effects of alpha(1)-adrenoceptor antagonists on intraurethral pressure in the prostatic urethra and intraluminal pressure in the vas deferens in anesthetized male dogs, and compared their tissue selectivity. Phenylephrine, an alpha(1)-adrenoceptor agonist, induced simultaneous increases in intraurethral and intraluminal pressure. Alfuzosin, naftopidil, prazosin, silodosin and tamsulosin dose-dependently inhibited both responses. Comparison of ED(50) values in both tissues showed that silodosin had the highest selectivity for the vas deferens (7.5-fold), followed by naftopidil (4.3-fold), alfuzosin (3.8-fold), tamsulosin (2.6-fold) and prazosin (2.5-fold). These results suggest that alpha(1)-adrenoceptor antagonists inhibit contraction of not only the urethra but also the vas deferens in a dose-dependent fashion, and that their high tissue selectivity for the vas deferens over the urethra may contribute to the incidence of abnormal ejaculation.
Noguchi
Yukiko
Y
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki, 305-8585, Japan.
Ohtake
Akiyoshi
A
Suzuki
Masanori
M
Sasamata
Masao
M
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004542:Ejaculation / Q000187:drug effects; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D008297:Male; D009281:Naphthalenes / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D010656:Phenylephrine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011224:Prazosin / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D011312:Pressure; D011467:Prostate; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D013449:Sulfonamides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects* / Q000378:metabolism; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D009281:Naphthalenes; D010879:Piperazines; D011799:Quinazolines; D013449:Sulfonamides; D010656:Phenylephrine; C047638:alfuzosin; C095285:silodosin; D000077409:Tamsulosin; C064357:naftopidil; D011224:Prazosin