Cevimeline (hydrochloride)是一种强效的直接作用muscarinic受体激动剂，具有口服生物利用度。
Cas No.:107220-28-0
Sample solution is provided at 25 µL, 10mM.
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Cevimeline (hydrochloride) is a potent direct-acting muscarinic receptor agonist with oral bioavailability [1]. Cevimeline (hydrochloride) can bind and activate M1 and M3 muscarinic receptors, and can cross the blood-brain barrier (BBB) to positively influence tau pathology and reduce the levels of amyloid-β (Aβ) peptide [2]. Cevimeline (hydrochloride) has been widely used to enhance the function of salivary glands and to increase the excitability of neurons in animal models[3].
In vitro, Cevimeline (hydrochloride) (10µM) treatment for 2 minutes significantly increased the calcium ion concentration within the rat parotid gland cells[4].
In vivo, Cevimeline (hydrochloride) treatment via oral administration at a dose of 10mg/kg/day for 7 days restored the level of AQP5 protein in the submandibular gland of rats, which had been decreased by parasympathectomy [5]. Oral administration of Cevimeline (hydrochloride) three times a day at a dose of 9mg/kg for 2 weeks reversed olanzapine-induced body weight gain and decreased feeding efficiency in female rats[6]. A single intraperitoneal injection of 10mg/kg dose of Cevimeline (hydrochloride) for 20 minutes significantly induced salivary secretion in diabetic mice and increased amylase activity[7].
References:
[1] Ono M, Takamura E, Shinozaki K, et al. Therapeutic effect of Cevimeline (hydrochloride) on dry eye in patients with Sjögren's syndrome: a randomized, double-blind clinical study[J]. American journal of ophthalmology, 2004, 138(1): 6-17.
[2] Oleksak P, Novotny M, Patocka J, et al. Neuropharmacology of Cevimeline (hydrochloride) and muscarinic drugs—focus on cognition and neurodegeneration[J]. International Journal of Molecular Sciences, 2021, 22(16): 8908.
[3] Ueda H, Mitoh Y, Ichikawa H, et al. Cevimeline (hydrochloride) enhances the excitability of rat superior salivatory neurons[J]. The Journal of Medical Investigation, 2009, 56(Supplement): 267-269.
[4] Ono K, Inagaki T, Iida T, et al. Distinct effects of Cevimeline (hydrochloride) and pilocarpine on salivary mechanisms, cardiovascular response and thirst sensation in rats[J]. Archives of oral biology, 2012, 57(4): 421-428.
[5] Li X, Azlina A, Karabasil M R, et al. Degradation of submandibular gland AQP5 by parasympathetic denervation of chorda tympani and its recovery by Cevimeline (hydrochloride), an M3 muscarinic receptor agonist[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2008, 295(1): G112-G123.
[6] Lian J, Deng C. The dosage-dependent effects of Cevimeline (hydrochloride) in preventing olanzapine-induced metabolic side-effects in female rats[J]. Pharmacology Biochemistry and Behavior, 2020, 191: 172878.
[7] ISHII H, NAKAGAWA Y, SHIGA T, et al. Effects of Cevimeline (hydrochloride) hydrochloride on salivary secretion in streptozotocin-induced diabetic Balb/cA mice[J]. ORAL THERAPEUTICS AND PHARMACOLOGY, 2001, 20(2): 86-91.
Cevimeline (hydrochloride)是一种强效的直接作用muscarinic受体激动剂，具有口服生物利用度[1]。Cevimeline (hydrochloride)能够结合并激活M1和M3 muscarinic受体，并能穿过血脑屏障（BBB），对tau蛋白病理产生积极影响，并降低amyloid-β (Aβ)肽的水平[2]。Cevimeline (hydrochloride)已被广泛用于增强唾液腺功能，并用于增加动物模型中神经元的兴奋性[3]。
在体外，使用10μM的Cevimeline (hydrochloride)处理大鼠腮腺细胞2分钟，显著增加了细胞内的钙离子浓度 [4]。
在体内，每日口服10mg/kg剂量的Cevimeline (hydrochloride)，连续7天，恢复了因副交感神经切除而降低的大鼠颌下腺中AQP5蛋白水平[5]。每日三次口服9mg/kg剂量的Cevimeline (hydrochloride)，持续2周，逆转了olanzapine诱导的雌性大鼠体重增加和摄食效率降低[6]。单次腹腔注射10mg/kg剂量的Cevimeline (hydrochloride)持续20分钟，显著诱导了糖尿病小鼠的唾液分泌，并增加了淀粉酶活性[7]。
| Cell experiment [1]: | |
Cell lines | Rat parotid gland cells |
Preparation Method | Rat parotid gland cells were immediately removed from deep anaesthesia of rats and placed in cold balanced salt solution (BSS) containing: 120mM NaCl, 5mM KCl, 1mM Na2HPO4, 2mM CaCl2, 1mM MgCl2, 10mM glucose, 20mM HEPES (adjusted to pH 7.4 by NaOH), and 0.5% bovine serum albumin. After mincing, the material was then digested for 30min at 37 °C with 50U/ml collagenase in BSS, and the suspension was gently passed through a pipette 10 times every 10min. After filtering through a 150μm nylon mesh, the cell preparations were loaded with 2μM fura-2AM, which was suspended in 10ml of BSS, and incubated for 30min at room temperature. After dispersing the cell preparation on poly-d-lysine-coated glass-bottom dishes, the dishes were mounted on the stage of an inverted fluorescence microscope and perfused with BSS at a rate of 1ml/min at 36 °C. The excitation of fura-2 was induced every second by an alternate illumination of 340 and 380nm light, and the resultant fluorescence (510-550nm) was collected using an objective lens and a silicon-intensified target camera. Different concentrations of Cevimeline (hydrochloride) (0, 1, 10, and 100µM) were applied to cells by superfusion. Record the calcium ion concentration data every two minutes. |
Reaction Conditions | 0, 1, 10, and 100µM; 2min |
Applications | Cevimeline (hydrochloride) treatment dose-dependently increased the calcium ion concentration within the rat parotid gland cells. |
| Animal experiment [2]: | |
Animal models | Male Sprague-Dawley rats |
Preparation Method | Male Sprague-Dawley rats (7 weeks old), weighing 170-190g, were kept in temperature-controlled (21°C-25°C) and humidity-maintained (40%-70%) rooms with a 12-h light/dark cycle. Water and food were provided freely. Cervical sympathetic trunk denervation (CSTD) or chorda tympani denervation (CTD) were performed under anesthesia with pentobarbital sodium (50mg/kg). Cevimeline (hydrochloride) (10mg/kg; p.o.), pilocarpine (0.3mg/kg; p.o.), or chloroquine diphosphate (50mg/kg; p.o.) was administered every day for 7 days starting from the 15th day after the operation. On the 21st day after the operation, the rats were killed and the submandibular glands were immediately dissected to determine AQP protein and mRNA levels. |
Dosage form | 10mg/kg/day for 7 days; p.o. |
Applications | Cevimeline (hydrochloride) treatment enhanced the levels of AQP5 protein and mRNA in the submandibular glands of rats after parasympathectomy. |
References: | |
| Cas No. | 107220-28-0 | SDF | |
| 别名 | 盐酸西维美林; AF102B hydrochloride | ||
| Canonical SMILES | C[C@@H](SC1)O[C@@]21CN3CCC2CC3.Cl | ||
| 分子式 | C10H17NOS•HCl | 分子量 | 235.8 |
| 溶解度 | DMF: 3 mg/ml,DMSO: 5 mg/ml,Ethanol: 5 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | Store at -20°C |
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.2409 mL | 21.2044 mL | 42.4088 mL |
| 5 mM | 848.2 μL | 4.2409 mL | 8.4818 mL |
| 10 mM | 424.1 μL | 2.1204 mL | 4.2409 mL |
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| % DMSO % % Tween 80 % saline | ||||||||||
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