Solifenacin-YM905-free-base-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESolifenacinCat. No.: HY-A0034CAS No.: 242478-37-1Synonyms: YM905 (free base)分式: CHNO分量: 362.46作靶点: mAChR作通路: GPCR/G Protein; Neuronal Signaling储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO

2、: 50 mg/mL (137.95 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.90 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (6.90 mM); Clear solution3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility:

3、2.5 mg/mL (6.90 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Solifenacin (YM905 free base)种新型的毒蕈碱受体拮抗剂，对 M1，M2 和 M3 受体的 pKi 值分别为 7.6,6.9 和 8.0。IC50 & Target pKi: 7.6 (M1 receptor), 6.9 (M2 receptor), 8.0 (M3 receptor) 1体外研究 Solifenacin is a novel muscarinic receptor antagonist with pKis of 7.60.056, 6.

4、90.034 and 8.00.021 forM1, M2 and M3 receptors, respectively. In murine submandibular gland cells, the antagonistic effects of 100nM Solifenacin and oxybutynin on Ca2+ mobilization evoked by varying doses of carbachol (CCh) areexamined. Solifenacin does not shift the CCh dose-activation curve in a p

5、arallel manner whereas oxybutyninshows insurmountable antagonism. The pKb values are obtained as 7.40.17 for Solifenacin and 8.80.21for oxybutynin 1.体内研究 Solifenacin reduces bladder responses by 40% at a dose of 210 nmol/kg (0.1 mg/kg) and abolishes them at2100 nmol/kg (1 mg/kg). In contrast, its in

6、hibitory effects on salivary and cardiac responses are only slight at630 nmol/kg (0.3 mg/kg), and reach 66% and 49%, respectively, at 2100 nmol/kg (1 mg/kg). At doses of 63and 210 nmol/kg (0.03 and 0.1 mg/kg), Solifenacin slightly increases saliva secretion 1. Solifenacin (0.01 to0.3 mg/kg i.v.) dos

7、e-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.PROTOCOLCell Assay 1 Cytosolic Ca2+ mobilization is determined in guinea pig detrusor cells. Briefly, single detrusor cells

8、areprepared from epithelium-free bladders, loaded with Fura 2, and suspended in phenol red-free Hanksbalanced salt solution supplemented with 20 mM HEPES (pH=7.4) and 0.1% bovine serum albumin (HBSS-H/B). A 490 L aliquot of the cell suspension is continuously stirred, kept at 28C and monitored for t

9、he ratioof fluorescence at 500 nm with excitation at 340 nm to that at 380 nm. To each aliquot, 5 L of test drug(including Solifenacin) and stimulant solutions are serially added with a 2 min interval, and the peak increaseover the level just before stimulation is used for data analysis 1.MCE has no

10、t independently confirmed the accuracy of these methods. They are for reference only.Animal Male rats (270 to 320 g) are used in this study. After the measurement of neurological deficits, cystometry isAdministration 2 performed. Briefly, conscious rats showing a moderate to severe neurological defi

11、cit (score: 4 to13) areplaced in a restraining cage. To facilitate drug (including Solifenacin) evaluation, only those animals showingurinary frequency are eligible for study. The bladder is emptied by drainage of urine through the catheter andthen continuously re-infused with saline. After stable v

12、oiding cycles are established, each rat receives asingle intravenous administration of test drug (including Solifenacin) at a volume of 1 ml/kg 2.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研

13、献 Neurourol Urodyn. 2017 Apr;36(4):1026-1033.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Ikeda K, et al. M(3) receptor antagonism by the novel antimuscarinic agent solifenacin in the urinary bladder and salivary gland. NaunynSchmiedebergs 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