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Solifenacin succinate

现货
Catalog No.
B1614
毒蕈碱受体拮抗剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 500.00
现货
50mg
¥ 600.00
现货
100mg
¥ 1,100.00
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1g
¥ 4,700.00
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Background

Solifenacin succinate is a quinuclidine and tetrahydroisoquinoline derivative and selective M3 muscarinic antagonist. It is used as a urological agent in the treatment of overactive bladder[1].

M3 muscarinic receptor is a muscarinic acetylcholine receptor encoded by the human gene CHRM3. Muscarinic M3 receptors are involved in various cellular responses, including breakdown of phosphoinositides, inhibition of adenylate cyclase and modulation of potassium channels through the action of G proteins[2].

In vitro: In radioligand receptor binding assay, the Kivalues of solifenacin for human muscarinic M1, M2, M3, M4and M5receptors were 26, 170, 12, 110 and 31 nM, respectively. In isolated rat urinary bladder, solifenacin competitively antagonized carbachol-induced contractions, with a pA2value of 7.44±0.09[3].In bladder smooth muscle cells and salivary gland cells isolated from rats, solifenacin and the other antimuscarinic drugs inhibited carbachol-induced increases in intracellular Ca2+levels in a concentration-dependent manner. ThepKi was 8.12for bladder smooth muscle cells, 3.6-fold more potent than that for salivary gland cells (pKi=7.57) [1].

In vivo: In anesthetized rats, solifenacin dose-dependently inhibited carbachol-induced intravesical pressure elevation and salivary secretion, and exhibited selectivity (3.7- to 6.5-fold) for urinary bladder over salivary gland [1]. In anesthetized rats, solifenacin and oxybutynin increased the maximum bladder capacity in a dose-dependent manner and also decreased the maximum intravesical pressure [3].In healthy young men, multidose study evaluated doses. In the single-dose of solifenacin succinate (5-, 10-, 20-, and 30-mg), mean time to maximal concentration and elimination half-life ranged from 3.3 to 4.8 and from 40.2 to 57.6 hours, respectively.In the multidose study, the ranges were 2.9 to 5.8 and 45.0 to 64.8, respectively. The single-dose administration was well tolerated. The common adverse events were dry mouth, blurred vision, and headache [4].

Clinical trials: In this phase 3 trial in patients with symptoms related to overactive bladder, treatment with solifenacin (5 mg or 10 mg, once daily) significantly improved all the major symptoms of overactive bladder including urgency, frequency and incontinence. Solifenacin (10 mg) decreased the frequency of nocturia. Solifenacin therapy has been associated with a favorable tolerability profile and low incidence of dry mouth, especially at the 5 mg starting dose [5].

References:
[1]. Ohtake A, Ukai M, Hatanaka T, et al. In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats[J]. European journal of pharmacology, 2004, 492(2): 243-250.
[2]. Yang J, Williams J A, Yule D I, et al. Mutation of carboxyl-terminal threonine residues in human m3 muscarinic acetylcholine receptor modulates the extent of sequestration and desensitization[J]. Molecular pharmacology, 1995, 48(3): 477-485.
[3]. Ohtake A, Saitoh C, Yuyama H, et al. Pharmacological characterization of a new antimuscarinic agent, solifenacin succinate, in comparison with other antimuscarinic agents[J]. Biological and Pharmaceutical Bulletin, 2007, 30(1): 54-58.
[4]. Smulders R A, Krauwinkel W J, Swart P J, et al. Pharmacokinetics and safety of solifenacin succinate in healthy young men[J]. The Journal of Clinical Pharmacology, 2004, 44(9): 1023-1033.
[5]. Cardozo L, Lisec M, Millard R, et al. Randomized, double-blind placebo controlled trial of the once daily antimuscarinic agent solifenacin succinate in patients with overactive bladder[J]. The Journal of urology, 2004, 172(5): 1919-1924.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt480.55
Cas No.242478-38-2
FormulaC27H32N2O6
Solubility≥24.05mg/mL in DMSO
Chemical Name[(3R)-1-azabicyclo[2.2.2]octan-3-yl] (1S)-1-phenyl-3,4-dihydro-1H-isoquinoline-2-carboxylate;butanedioic acid
SDFDownload SDF
Canonical SMILESC1CN2CCC1C(C2)OC(=O)N3CCC4=CC=CC=C4C3C5=CC=CC=C5.C(CC(=O)O)C(=O)O
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1,2]:

细胞系

膀胱平滑肌细胞,CEM人类白血病T细胞

溶解方法

该化合物在DMSO中的溶解度大于24.1mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

0.1 nM-1 μM

应用

在膀胱平滑肌细胞中,solifenacin以浓度依赖性方式抑制10 μM卡巴胆碱诱导的Ca2+动员。在CEM人类白血病T细胞中,YM905(10 nM-10 μM)显著减少了响应于10 μM Oxo-M处理的细胞数。YM905减弱10 μM Oxo-M诱导的c-fos mRNA表达的上调,尽管YM905在1或10 μM时对c-fos mRNA的基础表达没有影响。

动物实验 [1,3]:

动物模型

雌性Wistar大鼠,小鼠

给药剂量

静脉注射,0.03-1 mg/kg

应用

YM905 (0.03-1 mg/kg, i.v.)以剂量依赖性方式显著抑制膀胱内压升高。YM905 (0.1 mg/kg, i.v.)不影响唾液分泌。静脉注射0.3 mg/kg剂量的YM905具有约超过50%的抑制作用。相较于唾液反应,YM905对膀胱反应抑制作用更强,ID30和ID50值表明其对膀胱具有6.5倍和3.7倍的选择性。YM905有效抑制饲喂大鼠中约束应激诱导的粪便颗粒输出(ED50为4.0 mg/kg)和禁食大鼠的腹泻(ED50为1.7 mg/kg)。在小鼠中,YM905抑制5-羟色胺(5-HT)、前列腺素E2和蓖麻油诱导的分泌性腹泻,ED50分别为5.5、14和6.3 mg/kg,而对霍乱毒素诱导的肠道分泌没有显著影响。在痉挛便秘模型雪貂中,YM905(3、10 mg/kg)逆转吗啡降低的餐后排便。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Ohtake, A., Ukai, M., Hatanaka, T., Kobayashi, S., Ikeda, K., et, al (2004). In vitro and in vivo tissue selectivity profile of solifenacin succinate (YM905) for urinary bladder over salivary gland in rats. European journal of pharmacology, 492(2), 243-250.

[2]. Fujii, T., & Kawashima, K. (2000). YM905, a novel M 3 antagonist, inhibits Ca 2+ signaling and c-fos gene expression mediated via muscarinic receptors in human T cells. General Pharmacology: The Vascular System, 35(2), 71-75.

[3]. Kobayashi, S., Ikeda, K., Suzuki, M., Yamada, T., & Miyata, K. (2001). Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. The Japanese journal of pharmacology, 86(3), 281-288.

质量控制

化学结构

Solifenacin succinate