(S)-(+)-Dimethindene maleate is a highly selective muscarinic M2 receptor antagonist (pA2 = 7.86/7.74; pKi= 7.78)[1]. The muscarinic M2 receptor is a G protein-coupled receptor primarily distributed in the heart, and its activation can inhibit heart rate and myocardial contractility[2]. (S)-(+)-Dimethindene maleate is commonly used in research areas such as autonomic nervous regulation, cardiovascular and respiratory systems, and can assist other chemicals in creating extended pluripotent stem cells (EPSCs)[3,4].
In vitro, reprogramming goat fetal fibroblasts (GFFs) using LCDM medium containing (S)-(+)-Dimethindene maleate (2µM) successfully induced the generation of pluripotent goat induced pluripotent stem cells (giPSCs), which were capable of differentiating into the three germ layers in vitro[5]. Pretreatment of rabbit vas deferens with (S)-(+)-Dimethindene maleate (10µM) for 30-60min competitively antagonized the 4-Cl-McN-A-343-induced inhibition of neurogenic twitch contractions[1]. Culture of mouse embryonic stem cells (mESCs) for 3 days in LCDM medium containing (S)-(+)-Dimethindene maleate (2µM) converted them into mouse extended pluripotent stem cells (mEPSCs), and this medium could be used for subsequent routine passaging and culture[6].
References:
[1] Pfaff O, Hildebrandt C, Waelbroeck M, et al. The (S)-(+)-enantiomer of dimethindene: a novel M2-selective muscarinic receptor antagonist[J]. European Journal of Pharmacology, 1995, 286(3): 229-240.
[2] Saternos H C, Almarghalani D A, Gibson H M, et al. Distribution and function of the muscarinic receptor subtypes in the cardiovascular system[J]. Physiological Genomics, 2018, 50(1): 1-9.
[3] Xu J, Yu L, Guo J, et al. Generation of pig induced pluripotent stem cells using an extended pluripotent stem cell culture system[J]. Stem Cell Research & Therapy, 2019, 10(1): 193.
[4] Lanzafame A A, Christopoulos A, Mitchelson F. Cellular signaling mechanisms for muscarinic acetylcholine receptors[J]. Receptors and Channels, 2003, 9(4): 241-260.
[5] Liu F, Wang J, Yue Y, et al. Derivation of arbas cashmere goat induced pluripotent stem cells in LCDM with trophectoderm lineage differentiation and interspecies chimeric abilities[J]. International Journal of Molecular Sciences, 2023, 24(19): 14728.
[6] Zhu K, Liu Y, Fan C, et al. Etv5 safeguards trophoblast stem cells differentiation from mouse EPSCs by regulating fibroblast growth factor receptor 2[J]. Molecular Biology Reports, 2020, 47(12): 9259-9269.
(S)-(+)-Dimethindene maleate是一种具有高效选择性的毒蕈碱M2受体拮抗剂（pA2 = 7.86/7.74; pKi = 7.78）[1]。毒蕈碱M2受体是一种G蛋白偶联受体，主要分布于心脏，激活后能抑制心率和心肌收缩力[2]。(S)-(+)-Dimethindene maleate通常用于自主神经调节、心血管与呼吸系统等领域的研究，并可辅助其他化学物质以创建扩展多能干细胞（EPS）[3,4]。
在体外，用含有(S)-(+)-Dimethindene maleate（2μM）的LCDM培养基对山羊胎儿成纤维细胞（GFFs）进行重编程，成功诱导出具有多能性的山羊诱导多能干细胞（giPSCs），并能在体外分化为三个胚层[5]。(S)-(+)-Dimethindene maleate（10μM）预处理兔输精管30-60min，竞争性地拮抗了由4-Cl-McN-A-343诱导的神经源性抽搐抑制[1]。用含有(S)-(+)-Dimethindene maleate（2μM）的LCDM培养基培养小鼠胚胎干细胞（mESCs）3天，可将其转化为小鼠扩展多能干细胞（mEPSCs），并可使用该培养基进行后续的常规传代培养[6]。