Department of Pharmacology II, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Institute for Bioscience, Mukogawa Women's University, Nishinomiya, Japan.
Basic Clin Pharmacol Toxicol. 2024 Oct;135(4):451-463. doi: 10.1111/bcpt.14071. Epub 2024 Sep 1.
Several medications are commonly administered to older Japanese patients. Since some of them have not been included in previously developed scales to estimate the anticholinergic burden, we have developed a new muscarinic receptor binding-based anticholinergic burden scale. This study aimed to investigate the functional inhibitory effects of 60 medications, classified as anticholinergic burden scales 3 and 2 by the anticholinergic burden scale, on muscarinic receptor-mediated contractions in the bladder and ileum. The relaxation response induced by these drugs on isolated rat bladders and ileum smooth muscles constricted by carbachol was assessed using the organ bath method. All drugs inhibited smooth muscle contractile responses induced by the muscarinic receptor activation in a concentration-dependent manner in the rat bladder and ileum. Notably, variations were observed in the relaxation responses of the drugs, and the function EC values were positively correlated with the binding IC values in the bladder and ileum. The results of this study provide functional pharmacological evidence for the muscarinic receptor binding-based anticholinergic burden scale. Implementation of this scale may help reduce the risk of constipation and urinary retention, which are common side effects associated with anticholinergic drugs.
几种药物通常用于老年日本患者。由于其中一些药物未包含在先前开发的评估抗胆碱能负担的量表中，我们开发了一种新的基于毒蕈碱受体结合的抗胆碱能负担量表。本研究旨在研究 60 种药物的功能抑制作用，这些药物根据抗胆碱能负担量表被分类为抗胆碱能负担量表 3 和 2，作用于膀胱和回肠中的毒蕈碱受体介导的收缩。使用器官浴方法评估这些药物对乙酰胆碱引起的分离大鼠膀胱和回肠平滑肌收缩的松弛反应。所有药物以浓度依赖性方式抑制大鼠膀胱和回肠中由毒蕈碱受体激活引起的平滑肌收缩反应。值得注意的是，观察到药物的松弛反应存在差异，并且功能 EC 值与膀胱和回肠中的结合 IC 值呈正相关。本研究的结果为基于毒蕈碱受体结合的抗胆碱能负担量表提供了功能药理学证据。实施该量表可能有助于降低与抗胆碱能药物相关的常见副作用，如便秘和尿潴留的风险。
