[Duration of action of silodosin (KMD-3213) against phenylephrine-induced increase in intraurethral pressure in rats].
The duration of action of Silodosin (KMD-3213) against the phenylephrine-induced increase in intraurethral pressure in urethane-anesthetized rats was compared with that of tamsulosin hydrochloride. Silodosin, tamsulosin, or vehicle was orally administered to fasted male rats. Then, under urethane anesthesia, a cannula was inserted into the prostatic urethra. Phenylephrine, at a dose of 30 microg/kg, was infused (infusion rate: 36 ml/h; infusion time: 100 s/kg) via the femoral vein at 12 h, 18 h, or 24 h after administration of the study drug, and the intraurethral pressure in the prostate region was measured. Although the plasma silodosin concentration would have resolved within a few hours, silodosin significantly inhibited the phenylephrine-induced increase in intraurethral pressure (versus the vehicle-treated group) at 12 h, 18 h, and 24 h after its oral administration (at doses of 100 microg/kg and above, 1000 microg/kg and above, and 3000 microg/kg, respectively). On the other hand, tamsulosin hydrochloride showed no inhibitory action at 24 h after its oral administration at doses up to 3000 microg/kg. Thus, silodosin inhibits the phenylephrine-induced increase in intraurethral pressure for a longer time than tamsulosin hydrochloride.
Kobayashi
Mamoru
M
Pharmacology Research Laboratory, R&D, Kissei Pharmaceutical Co., Ltd., Azumino City, Japan. mamoru_kobayashi@pharm.kissei.co.jp
Tatemichi
Satoshi
S
Kobayashi
Kumi
K
Imamura
Takahiro
T
Maruyama
Itaru
I
Yamazaki
Yoshinobu
Y
Shibata
Nobuo
N
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D007211:Indoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D010656:Phenylephrine / Q000037:antagonists & inhibitors*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D013449:Sulfonamides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D000077409:Tamsulosin; D013997:Time Factors; D014521:Urethra / Q000187:drug effects*
D058668:Adrenergic alpha-1 Receptor Antagonists; D000317:Adrenergic alpha-Antagonists; D007211:Indoles; D013449:Sulfonamides; D010656:Phenylephrine; C095285:silodosin; D000077409:Tamsulosin