Effects of tamsulosin on hypogastric nerve stimulation-induced intraurethral pressure elevation in male and female dogs under anesthesia.
The aim of the present study was to investigate the effects of tamsulosin, an alpha(1)-adrenoceptor antagonist, on hypogastric nerve stimulation-induced intraurethral pressure elevation in anesthetized male and female dogs and to evaluate sex differences in these effects. Additionally, the effects of tamsulosin were also compared with those of other alpha(1)-adrenoceptor antagonists, namely prazosin, naftopidil and urapidil. Tamsulosin dose-dependently inhibited hypogastric nerve stimulation-induced intraurethral pressure elevation, with doses required to induce 50% inhibition of the elevation (ED(50) values) of 0.72 and 0.74 microg/kg i.v. in anesthetized male and female dogs, respectively. Mean arterial blood pressure slightly decreased after administration of tamsulosin at a dose which inhibited intraurethral pressure elevation almost completely. Prazosin, naftopidil and urapidil also inhibited increases in intraurethral pressure in a dose-dependent fashion, but caused decreases in mean arterial blood pressure at the same doses. The estimated rank order of inhibitory potency for urethral response was tamsulosin>prazosin>naftopidil=urapidil. In conclusion, tamsulosin dose-dependently inhibited increases in intraurethral pressure with little effect on mean arterial blood pressure in both male and female dogs, and these effects were almost equipotent. These results indicate that tamsulosin will be useful in the treatment of dysuria associated with lower urinary tract symptoms in women as well as men.
Ohtake
Akiyoshi
A
Pharmacology Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. ohtake@yamanouchi.co.jp
Sato
Shuichi
S
Saitoh
Chikashi
C
Yuyama
Hironori
H
Sasamata
Masao
M
Miyata
Keiji
K
D058668:Adrenergic alpha-1 Receptor Antagonists; D000818:Animals; D004285:Dogs; D005260:Female; D007001:Hypogastric Plexus / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009281:Naphthalenes / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011312:Pressure; D012737:Sex Factors; D013449:Sulfonamides / Q000494:pharmacology*; D000077409:Tamsulosin; D014521:Urethra / Q000187:drug effects* / Q000502:physiology
D058668:Adrenergic alpha-1 Receptor Antagonists; D009281:Naphthalenes; D010879:Piperazines; D013449:Sulfonamides; C015568:urapidil; D000077409:Tamsulosin; C064357:naftopidil; D011224:Prazosin