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标题：Effects of Intravenously and Orally Administered Solifenacin Succinate (YM905) on Carbachol-Induced Intravesical Pressure Elevation and Salivary Secretion in Mice
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作者：Hiroko Okutsu ; Yukiko Noguchi ; Akiyoshi Ohtake 等
期刊名称：Biological and Pharmaceutical Bulletin
印刷版ISSN：0918-6158
电子版ISSN：1347-5215
出版年度：2007
卷号：30
期号：12
页码：2324-2327
DOI：10.1248/bpb.30.2324
出版社：The Pharmaceutical Society of Japan
摘要：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 ID₅₀ 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 ID₅₀ 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.
关键词：solifenacin;muscarinic M3 receptor;oral administration;intravesical pressure elevation;salivary secretion;mouse