Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarcted rats.
Solifenacin succinate [YM905, (+)-(1S,3'R)-quinuclidin-3'-yl 1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate monosuccinate] is a novel muscarinic receptor antagonist. We examined the effects of solifenacin and two other muscarinic receptor antagonists, tolterodine and propiverine, on detrusor overactivity in cerebral infarcted rats. Evaluation was done under conscious conditions using cystometry 1 day after middle cerebral artery occlusion. The cerebral infarcted rats showed decreases in bladder capacity and voided volume and an increase in residual volume, but no change in micturition pressure. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.
Suzuki
Masanori
M
Applied Pharmacology Research, Pharmacology Laboratories, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. suzuki_m@yamanouchi.co.jp
Ohtake
Akiyoshi
A
Yoshino
Taiji
T
Yuyama
Hironori
H
Hayashi
Aska
A
Ukai
Masashi
M
Okutsu
Hiroko
H
Noguchi
Yukiko
Y
Sato
Shuichi
S
Sasamata
Masao
M
D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology; D001561:Benzilates / Q000494:pharmacology; D003408:Cresols / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000503:physiopathology; D010665:Phenylpropanolamine / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D000068737:Tolterodine Tartrate; D001743:Urinary Bladder / Q000187:drug effects* / Q000503:physiopathology; D001750:Urinary Bladder, Neurogenic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology
D001559:Benzhydryl Compounds; D001561:Benzilates; D003408:Cresols; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D010665:Phenylpropanolamine; C015586:propiverine; D000068737:Tolterodine Tartrate; D000069464:Solifenacin Succinate