Effects of Intravenously and Orally Administered Solifenacin Succinate (YM905) on Carbachol-Induced Intravesical Pressure Elevation and Salivary Secretion in Mice

• Published in: Biological & Pharmaceutical Bulletin Vol. 30; no. 12; pp. 2324 - 2327
• Main Authors: Okutsu, Hiroko, Noguchi, Yukiko, Ohtake, Akiyoshi, Suzuki, Masanori, Sato, Shuichi, Sasamata, Masao
• Format: Journal Article
• Language: English
• Published: Japan The Pharmaceutical Society of Japan 01.12.2007; Pharmaceutical Society of Japan; Japan Science and Technology Agency
• Subjects: Administration, Oral; Anesthesia; Animals; Blood Pressure - drug effects; Carbachol - antagonists & inhibitors; Carbachol - pharmacology; Injections, Intravenous; intravesical pressure elevation; Mice; mouse; Muscarinic Agonists - pharmacology; Muscarinic Antagonists - administration & dosage; Muscarinic Antagonists - pharmacology; muscarinic M3 receptor; oral administration; Quinuclidines - administration & dosage; Quinuclidines - pharmacology; salivary secretion; Salivation - drug effects; solifenacin; Solifenacin Succinate; Tetrahydroisoquinolines - administration & dosage; Tetrahydroisoquinolines - pharmacology
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.30.2324

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.