Effects of intravenously and orally administered solifenacin succinate (YM905) on carbachol-induced intravesical pressure elevation and salivary secretion in mice.
Solifenacin succinate is a novel muscarinic receptor antagonist used for the treatment of overactive bladder (OAB). We investigated the effects of solifenacin by oral and intravenous administration on carbachol (CCh)-induced intravesical pressure (IVP) elevation and compared its efficacy with that on CCh-induced salivary secretion in anesthetized mice. Additionally, we also investigated the change in effects between single and repeated oral administration of solifenacin on CCh-induced IVP elevation. Results showed that intravenous administration of solifenacin dose-dependently inhibited the IVP elevation and salivary secretion. The ratio of bladder response to salivary response (ratio of ID(50) values) was 2.1. Oral administration of solifenacin (0.3-30 mg/kg) also inhibited CCh-induced IVP elevation and salivary secretion. Although inhibition of these responses by solifenacin (10, 30 mg/kg) was comparable at early time points (0.5 and 1 h after administration at 10 mg/kg and 0.5 to 2 h after administration at 30 mg/kg), inhibition of CCh-induced IVP elevation was stronger at later time points (2 to 8 h after administration at 10 mg/kg and 4 to 24 h after administration at 30 mg/kg). No significant difference in ID(50) values for IVP elevation was observed between single and repeated (11 d) oral administration of solifenacin (1-30 mg/kg), suggesting no change in efficacy on chronic administration. In conclusion, intravenous and oral solifenacin inhibits CCh-induced IVP elevation more potently than salivary secretion. These results provide further evidence for the clinical use of solifenacin as a promising therapeutic drug for OAB with a low incidence of dry mouth.
Okutsu
Hiroko
H
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. hiroko.okutsu@jp.astellas.com
Noguchi
Yukiko
Y
Ohtake
Akiyoshi
A
Suzuki
Masanori
M
Sato
Shuichi
S
Sasamata
Masao
M
D000284:Administration, Oral; D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002217:Carbachol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D007275:Injections, Intravenous; D051379:Mice; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology*; D012472:Salivation / Q000187:drug effects*; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*
D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D002217:Carbachol; D000069464:Solifenacin Succinate