In vitro activity: Solifenacin (formerly known as YM905) is a novel and potent muscarinic receptor antagonist with pKis of 7.6, 6.9 and 8.0 for M1, M2 and M3 receptors, respectively. Solifenacin increased bladder capacity and voided volume at doses of 0.03 mg/kg i.v. or more. Tolterodine increased bladder capacity and voided volume at 0.03 and 0.1 mg/kg i.v., while propiverine increased bladder capacity and voided volume at 1 mg/kg i.v. and at 0.3 and 1 mg/kg i.v., respectively. In contrast, none of the three drugs affected residual volume or micturition pressure. These results suggest that solifenacin may improve detrusor overactivity without causing urinary retention and may be a promising drug in the treatment of patients with overactive bladder syndrome.

Kinase Assay: Solifenacin is a novel muscarinic receptor antagonist with pKis of 7.6±0.056, 6.9±0.034 and 8.0±0.021 for M1, M2 and M3 receptors, respectively.

Cell Assay: 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 pKb values are obtained as 7.4±0.17 for Solifenacin and 8.8±0.21 for oxybutynin. Cytosolic Ca2+ mobilization is determined in guinea pig detrusor cells. Briefly, single detrusor cells are prepared from epithelium-free bladders, loaded with Fura 2, and suspended in phenol red-free Hanks’ balanced salt solution supplemented with 20 mM HEPES (pH=7.4) and 0.1% bovine serum albumin (HBSS-H/B). A 490 μL aliquot of the cell suspension is continuously stirred, kept at 28°C and monitored for the ratio of fluorescence at 500 nm with excitation at 340 nm to that at 380 nm. To each aliquot, 5 μL of test drug (including Solifenacin) and stimulant solutions are serially added with a 2 min interval, and the peak increase over the level just before stimulation is used for data analysis.