Obara Keisuke, Tanaka Yoshio
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toho University.
Yakugaku Zasshi. 2021;141(2):245-254. doi: 10.1248/yakushi.20-00212.
Distigmine bromide (distigmine) is a carbamate cholinesterase (ChE) inhibitor, which is mainly used for the treatment of myasthenia gravis. Distigmine is also used in Japan for the treatment for underactive bladder and glaucoma. The effectiveness of distigmine for underactive bladder treatment has been confirmed by many clinical reports, and this effect is thought to be caused by potentiating urinary bladder smooth muscle contraction due to inhibition of acetylcholine degradation during micturition. However, the pharmacological effects of distigmine on urinary bladder smooth muscle have not been well studied. The most distinctive pharmacological feature of distigmine is that it shows long-lasting effects than other ChE inhibitors; however, few studies have investigated the persistence of the enhancing effect of distigmine on the contractile function of urinary bladder smooth muscle. Moreover, this mechanism remains unclear. In this review, we present our findings on the mechanism of the potentiating effect of distigmine on isolated guinea pig urinary bladder smooth muscle contraction. We also discuss the long-lasting potentiating effect of distigmine on urinary bladder motility and the mechanism of these effects using guinea pig urinary bladder smooth muscle in vivo and in vitro. In addition, we present our investigations on the long-lasting mechanism of distigmine using recombinant human acetylcholinesterase.
溴化双斯的明（双斯的明）是一种氨基甲酸酯类胆碱酯酶（ChE）抑制剂，主要用于治疗重症肌无力。双斯的明在日本还用于治疗膀胱活动低下和青光眼。许多临床报告已证实双斯的明治疗膀胱活动低下的有效性，这种作用被认为是由于在排尿过程中抑制乙酰胆碱降解从而增强膀胱平滑肌收缩所致。然而，双斯的明对膀胱平滑肌的药理作用尚未得到充分研究。双斯的明最显著的药理特性是其作用持续时间比其他胆碱酯酶抑制剂长；然而，很少有研究探讨双斯的明对膀胱平滑肌收缩功能增强作用的持续性。此外，该机制仍不清楚。在本综述中，我们展示了关于双斯的明对离体豚鼠膀胱平滑肌收缩增强作用机制的研究结果。我们还使用豚鼠膀胱平滑肌在体内和体外讨论了双斯的明对膀胱运动的持久增强作用及其机制。此外，我们展示了使用重组人乙酰胆碱酯酶对双斯的明持久机制的研究。
