Solifenacin (YM905)

Cell experiment:

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[1].

Animal experiment:

Male rats (270 to 320 g) are used in this study. After the measurement of neurological deficits, cystometry is performed. Briefly, conscious rats showing a moderate to severe neurological deficit (score: 4 to13) are placed in a restraining cage. To facilitate drug (including Solifenacin) evaluation, only those animals showing urinary frequency are eligible for study. The bladder is emptied by drainage of urine through the catheter and then continuously re-infused with saline. After stable voiding cycles are established, each rat receives a single intravenous administration of test drug (including Solifenacin) at a volume of 1 ml/kg[2].

References:

[1]. Ikeda K, et al. M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. Naunyn Schmiedebergs Arch Pharmacol. 2002 Aug;366(2):97-103.
[2]. Suzuki M, et al. Effects of solifenacin succinate (YM905) on detrusor overactivity in conscious cerebral infarctedrats. Eur J Pharmacol. 2005 Apr 4;512(1):61-6.