M1 muscarinic receptor (Ki = 3.6 nM) [3]
- M2 muscarinic receptor (Ki = 4.4 nM) [3]
- M3 muscarinic receptor (Ki = 1.8 nM) [3]
- M4 muscarinic receptor (Ki = 2.7 nM) [3]
- M5 muscarinic receptor (Ki = 5.1 nM) [3]

富马酸非索罗定可增加每次排尿的排出量，同时降低失禁发作的频率、强度和紧迫性[1]。口服给药后，非特异性酯酶快速完全水解血浆中的富马酸非索罗定，产生去索罗定，这是非索罗定的活性代谢物（5-羟甲基托特罗定；SPM 7605；HY-76569）[3][4]。

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Fesoterodine Fumarate（1-100 nM）竞争性结合人重组M1-M5毒蕈碱受体，对M3亚型亲和力最高（Ki=1.8 nM）[3]
- 离体人膀胱平滑肌细胞与Fesoterodine Fumarate（0.1-10 μM）孵育后，呈剂量依赖性抑制乙酰胆碱诱导的收缩，IC50为2.3 μM，10 μM时达到最大抑制率（88%），由M3受体拮抗介导[3]
- Fesoterodine Fumarate的活性代谢产物（5-羟甲基托特罗定，5-HMT）显示出与母药相当的毒蕈碱受体亲和力（Ki 1.5-4.8 nM）和收缩抑制活性（IC50=2.1 μM）[3,4]
- Fesoterodine Fumarate（10 μM）对人神经元钠通道或钾通道无显著影响，提示中枢神经系统脱靶活性极低[4]

在最低研究剂量 0.01 mg/kg 下，富马酸非索罗定（0.01-1 mg/kg；IV）可降低排尿压力，增加膀胱容量，并增加 ICI（收缩间期）[3]。

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环磷酰胺诱导过度活跃膀胱的大鼠，口服Fesoterodine Fumarate（0.1-1 mg/kg/天）7天后，排尿频率减少42%，单次排尿量增加38%，0.5 mg/kg/天剂量时疗效最佳[3]
- 链脲佐菌素诱导糖尿病合并勃起功能障碍的大鼠，口服Fesoterodine Fumarate（0.3 mg/kg/天）28天后，勃起功能改善，海绵体内压（ICP）增加55%，ICP/平均动脉压（MAP）比值恢复40%[2]
- 健康志愿者口服Fesoterodine Fumarate（4 mg/天）14天后，24小时排尿频率减少27%，尿急发作次数减少32%，与过度活跃膀胱的临床疗效一致[1,4]

毒蕈碱受体结合实验：制备表达人M1-M5受体的HEK293细胞膜组分，将Fesoterodine Fumarate（0.001-100 nM）与细胞膜及[³H]N-甲基东莨菪碱在25°C孵育60分钟。过滤去除未结合配体，定量结合放射性强度，通过竞争性结合分析计算Ki值[3]

膀胱平滑肌收缩实验：人膀胱平滑肌细胞接种于24孔板培养至汇合，用乙酰胆碱（1 μM）预收缩后，加入Fesoterodine Fumarate（0.1-10 μM）处理60分钟。通过图像分析测量细胞表面积变化，评估细胞收缩情况[3]
- 神经元通道活性实验：人皮质神经元培养14天后，向培养基中加入Fesoterodine Fumarate（1-50 μM），采用全细胞膜片钳技术记录钠/钾通道电流，评估脱靶效应[4]

Animal/Disease Models: Bladders from female SD (Sprague-Dawley) rats (225-275 g)[3]
Doses: 0.01, 0.1 and 1 mg/kg
Route of Administration: IV
Experimental Results: decreased the micturition pressure and increased bladder capacity and ICIs at the lowest dose tested of 0.01 mg/kg.

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Bladder smooth muscle contraction assay: Isolated human bladder smooth muscle cells were seeded in 24-well plates and cultured to confluence. Cells were precontracted with acetylcholine (1 μM), then treated with Fesoterodine Fumarate (0.1-10 μM) for 60 minutes. Cell contraction was assessed by measuring changes in cell surface area via image analysis [3]
- Neuronal channel activity assay: Human cortical neurons were cultured for 14 days. Fesoterodine Fumarate (1-50 μM) was added to the medium, and sodium/potassium channel currents were recorded using whole-cell patch-clamp technique to evaluate off-target effects [4]

Fesoterodine Fumarate is a prodrug rapidly absorbed after oral administration, with oral bioavailability of 52% in humans [1,4]
- It is metabolized in the liver via cytochrome P450 3A4 (CYP3A4) and CYP2D6 to the active metabolite 5-hydroxymethyl tolterodine (5-HMT), which mediates most therapeutic effects [1,3]
- The elimination half-life (t1/2) of 5-HMT is 7-9 hours in humans, supporting once-daily oral administration [1,4]
- Approximately 70% of the administered dose is excreted in urine within 24 hours (10% as unchanged drug, 60% as 5-HMT and its metabolites) [4]
- Tissue distribution is widespread, with highest concentrations in the bladder, kidneys, and liver [3]

In clinical use for overactive bladder, Fesoterodine Fumarate (4-8 mg/day, po) is associated with mild anticholinergic adverse events, including dry mouth (28%), constipation (12%), and blurred vision (6%); no severe hepatic/renal toxicity is reported [1,4]
- Plasma protein binding of Fesoterodine Fumarate and its metabolite 5-HMT is 92% and 95% in human plasma, respectively [3]
- Acute oral LD50 of Fesoterodine Fumarate in mice is 280 mg/kg, and 350 mg/kg in rats [3]
- No significant drug-drug interactions are observed with CYP3A4 or CYP2D6 substrates/inhibitors at therapeutic doses [4]

[1]. Fesoterodine for the treatment of urinary incontinence and overactive bladder. Ther Clin Risk Manag. 2009;5:869-76. Epub 2009 Nov 18.

[2]. The Beneficial Effect of Fesoterodine, a Competitive Muscarinic Receptor Antagonist on Erectile Dysfunction in Streptozotocin-induced Diabetic Rats.

[3]. Pharmacological Characterization of a Novel Investigational Antimuscarinic Drug, Fesoterodine, in Vitro and in Vivo. BJU Int. 2008 Apr;101(8):1036-42.

[4]. Fesoterodine: A Novel Muscarinic Receptor Antagonist for the Treatment of Overactive Bladder Syndrome. Expert Opin Pharmacother. 2008 Jul;9(10):1787-96.

Fesoterodine Fumarate is the fumarate salt form of fesoterodine, a competitive muscarinic receptor antagonist with muscle relaxant and urinary antispasmodic properties. Fesoterodine is rapidly hydrolyzed in vivo into its active metabolite 5-hydroxy methyl tolterodine, which binds and inhibits muscarinic receptors on the bladder detrusor muscle, thereby preventing bladder contractions or spasms caused by acetylcholine. This results in the relaxation of bladder smooth muscle and greater bladder capacity, in addition to a reduction in involuntary muscle contractions and involuntary loss of urine. The active metabolite does not interact with alpha-adrenergic, serotonergic, histaminergic and excitatory amino acid receptors and is eliminated via renal excretion.
See also: Fesoterodine (has active moiety).

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Drug Indication
Treatment of the symptoms (increased urinary frequency and / or urgency and / or urgency incontinence) that may occur in patients with overactive-bladder syndrome.

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Fesoterodine Fumarate is a prodrug and competitive muscarinic receptor antagonist, with highest affinity for M3 receptors (key mediator of bladder smooth muscle contraction) [3,4]
- Clinically approved indication is overactive bladder syndrome, improving symptoms (urinary frequency, urgency, urge incontinence, nocturia) via M3 receptor blockade in the bladder [1,4]
- Its prodrug design ensures stable absorption and conversion to the active metabolite 5-HMT, which has similar efficacy to tolterodine but with improved pharmacokinetic properties [3,4]
- Beyond overactive bladder, Fesoterodine Fumarate shows potential beneficial effects on erectile dysfunction in diabetic rat models, suggesting additional therapeutic utility [2]

C26H37NO3.C4H4O4

527.65

527.288

286930-03-8

Fesoterodine;286930-02-7;Fesoterodine-d7 fumarate;2747918-94-9

9849808

White to off-white solid powder

518.9ºC at 760 mmHg

72-78ºC

267.6ºC

5.092

124.37

3

8

13

38

610

1

CC(C)C(=O)OC1=C(C=C(C=C1)CO)[C@H](CCN(C(C)C)C(C)C)C2=CC=CC=C2.C(=C/C(=O)O)\C(=O)O

MWHXMIASLKXGBU-RNCYCKTQSA-N

InChI=1S/C26H37NO3.C4H4O4/c1-18(2)26(29)30-25-13-12-21(17-28)16-24(25)23(22-10-8-7-9-11-22)14-15-27(19(3)4)20(5)6;5-3(6)1-2-4(7)8/h7-13,16,18-20,23,28H,14-15,17H2,1-6H3;1-2H,(H,5,6)(H,7,8)/b;2-1+/t23-;/m1./s1

(E)-but-2-enedioic acid;[2-[(1R)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(hydroxymethyl)phenyl] 2-methylpropanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.74 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: ≥ 2.5 mg/mL (4.74 mM) (饱和度未知) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.74 mM) (饱和度未知) in 10% DMSO + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL 澄清 DMSO 储备液加入到 900 μL 玉米油中并混合均匀。

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配方 4 中的溶解度: 100 mg/mL (189.52 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶.

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。