Effects of Intravenously and Orally Administered Solifenacin Succinate (YM905) on Carbachol-Induced Intravesical Pressure Elevation and Salivary Secretion in Mice(Pharmacology)
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概要
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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 (0.3-30mg/kg) also inhibited CCh-induced IVP elevation and salivary secretion. Although inhibition of these responses by solifenacin (10, 30mg/kg) was comparable at early time points (0.5 and 1h after administration at 10mg/kg and 0.5 to 2h after administration at 30mg/kg), inhibition of CCh-induced IVP elevation was stronger at later time points (2 to 8h after administration at 10mg/kg and 4 to 24h after administration at 30mg/kg). No significant difference in ID_<50> values for IVP elevation was observed between single and repeated (11d) oral administration of solifenacin (1-30mg/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.
- 2007-12-01
著者
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SASAMATA Masao
Applied Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc.
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Sasamata Masao
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Sasamata Masao
Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Suzuki Masanori
Pharmacology Research Labs. Drug Discovery Research Astellas Pharma Inc.
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OKUTSU Hiroko
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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NOGUCHI Yukiko
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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OHTAKE Akiyoshi
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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SATO Shuichi
Pharmacology Research Labs., Drug Discovery Research, Astellas Pharma Inc.
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Okutsu Hiroko
Pharmacology Research Labs. Drug Discovery Research Astellas Pharma Inc.
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Noguchi Yukiko
Pharmacology Research Labs. Drug Discovery Research Astellas Pharma Inc.
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Sato Shuichi
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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Ohtake Akiyoshi
Applied Pharmacology Research Laboratories Drug Discovery Research Astellas Pharma Inc.
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- Effects of Intravenously and Orally Administered Solifenacin Succinate (YM905) on Carbachol-Induced Intravesical Pressure Elevation and Salivary Secretion in Mice(Pharmacology)
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