Cevimeline is a potent direct-acting muscarinic receptor agonist with oral bioavailability [1]. Cevimeline 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 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 (10µM) treatment for 2 minutes significantly increased the calcium ion concentration within the rat parotid gland cells[4].
In vivo, Cevimeline 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 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 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 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 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 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 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, 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 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 on salivary secretion in streptozotocin-induced diabetic Balb/cA mice[J]. ORAL THERAPEUTICS AND PHARMACOLOGY, 2001, 20(2): 86-91.
Cevimeline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，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，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]。