Center for Pharma-Food Research (CPFR), Graduate School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan.
Geriatr Gerontol Int. 2023 Jul;23(7):558-564. doi: 10.1111/ggi.14619. Epub 2023 Jun 14.
The present study aimed to develop a pharmacological evidence-based anticholinergic burden scale (ABS) through a direct assessment of muscarinic receptor-binding activities of 260 medications commonly used in older adults.
The muscarinic receptor-binding activities of 260 drugs were assessed by the displacement of specific [N-methyl- H]scopolamine methyl chloride binding in the rat brain. The maximum blood concentrations (C ) of drugs after their administration to subjects were cited from their interview forms.
In total, 96 of 260 drugs displayed concentration-dependent muscarinic receptor binding in rat brain. Based on muscarinic receptor-binding activity (IC ) and C after the administration at clinical doses in humans, we rated ABS 3 (strong) for 33 drugs and ABS 2 (moderate) for 37 drugs. There was an approximate similarity between muscarinic receptor-binding activities (IC ) and C of 33 drugs (ABS 3) after their administration at clinical doses in humans. Furthermore, 26 drugs were defined as ABS 1 (weak) by muscarinic receptor-binding activity. The remaining 164 drugs exhibited slight or no significant muscarinic receptor-binding activities at high concentration of 100 μM, and they were defined as ABS 0. There was a marked similarity for 28 drugs (ABS 3) between the present ABS data and their previous scoring data in the literature.
To our knowledge, the present study developed the first comprehensive pharmacological evidence-based ABS of drugs based on muscarinic receptor-binding activity, which provides guidance as to which drugs may be discontinued to reduce anticholinergic burden. Geriatr Gerontol Int 2023; 23: 558-564.
本研究旨在通过直接评估 260 种常用于老年人的药物对毒蕈碱受体结合活性，开发一种基于药理学的抗胆碱能负担量表（ABS）。
通过特异性 [N-甲基- H] 东莨菪碱氯化物在大鼠脑中的置换来评估 260 种药物的毒蕈碱受体结合活性。从访谈表中引用药物在受试者给药后的最大血药浓度（C）。
在 260 种药物中，共有 96 种显示出与大鼠脑内毒蕈碱受体的浓度依赖性结合。基于在人类临床剂量给药后的毒蕈碱受体结合活性（IC）和 C，我们对 33 种药物评为 ABS 3（强），对 37 种药物评为 ABS 2（中）。在人类临床剂量给药后，33 种药物（ABS 3）的毒蕈碱受体结合活性（IC）和 C 之间存在近似相似性。此外，26 种药物根据毒蕈碱受体结合活性被定义为 ABS 1（弱）。其余 164 种药物在 100μM 的高浓度下表现出轻微或没有明显的毒蕈碱受体结合活性，被定义为 ABS 0。在本 ABS 数据和文献中之前的评分数据之间，有 28 种药物（ABS 3）存在明显的相似性。
据我们所知，本研究基于毒蕈碱受体结合活性开发了第一个全面的药物基于药理学的 ABS，为减少抗胆碱能负担应停用哪些药物提供了指导。老年医学与老年病学杂志 2023；23：558-564。
