Solifenacin

Solifenacin (YM905 free base) is a novel muscarinic receptor antagonist with pK_is of 7.6, 6.9 and 8.0 for M₁, M₂ and M₃ receptors, respectively. IC50 & Target: pKi: 7.6 (M₁ receptor), 6.9 (M₂ receptor), 8.0 (M₃ receptor)^[1] In Vitro: Solifenacin is a novel muscarinic receptor antagonist with pK_is of 7.6±0.056, 6.9±0.034 and 8.0±0.021 for M1, M2 and M3 receptors, respectively. In murine submandibular gland cells, the antagonistic effects of 100 nM Solifenacin and oxybutynin on Ca²⁺ mobilization evoked by varying doses of carbachol (CCh) are examined. Solifenacin does not shift the CCh dose-activation curve in a parallel manner whereas oxybutynin shows insurmountable antagonism. The pK_b values are obtained as 7.4±0.17 for Solifenacin and 8.8±0.21 for oxybutynin^[1]. In Vivo: Solifenacin reduces bladder responses by 40% at a dose of 210 nmol/kg (0.1 mg/kg) and abolishes them at 2100 nmol/kg (1 mg/kg). In contrast, its inhibitory effects on salivary and cardiac responses are only slight at 630 nmol/kg (0.3 mg/kg), and reach 66% and 49%, respectively, at 2100 nmol/kg (1 mg/kg). At doses of 63 and 210 nmol/kg (0.03 and 0.1 mg/kg), Solifenacin slightly increases saliva secretion^[1]. Solifenacin (0.01 to 0.3 mg/kg i.v.) dose-dependently increases bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more, but does not affect residual volume or micturition pressure at any dose tested^[2].