Aim
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.
Methods
The muscarinic receptor‐binding activities of 260 drugs were assessed by the displacement of specific [N‐methyl‐3H]scopolamine methyl chloride binding in the rat brain. The maximum blood concentrations (Cmax) of drugs after their administration to subjects were cited from their interview forms.
Results
In total, 96 of 260 drugs displayed concentration‐dependent muscarinic receptor binding in rat brain. Based on muscarinic receptor‐binding activity (IC50) and Cmax 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 (IC50) and Cmax 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.
Conclusions
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.
Regulation of arterial tone by perivascular adipose tissue (PVAT) differs between sexes. In male SHRSP.Z-<i>Lepr</i><sup><i>fa</i></sup>/IzmDmcr rats (SHRSP.ZF), PVAT exerts a compensatory relaxation effect for the loss of endothelium-mediated vasorelaxation, which occurs during the early stages of metabolic syndrome. However, this effect deteriorates by 23 weeks of age. Here, therefore, we compared the effects of PVAT in female and male SHRSP.ZF. Acetylcholine-induced relaxation in superior mesenteric artery without PVAT did not differ between 23-week-old females and males. However, the presence of PVAT enhanced relaxation in 23-week-old females, but not in males. The mRNA levels of angiotensin II type 1 receptor (AT1R) in PVAT did not differ between sexes, but AT1R-associated protein (ATRAP) and apelin levels were higher in females than in males. We observed a positive relationship between differences in artery relaxation with and without PVAT and ATRAP or apelin mRNA levels. In 30-week-old females, PVAT-enhanced relaxation disappeared, and mRNA levels of AT1R increased, while apelin levels decreased compared to 23-week-old females. These results demonstrated that in SHRSP.ZF, PVAT compensation for endothelium dysfunction extended to older ages in females than in males. Apelin and AT1R/ATRAP expression in PVAT may be predictors of favorable effects.
Intracerebral hemorrhage (ICH) is caused by the rupture of blood vessels in the brain. The excessive activation of glial cells and the infiltration of numerous inflammatory cells are observed during bleeding. Thrombin is a key molecule that triggers neuroinflammation in the ICH brain. In this study, we focused on lipoxin A4 (LXA4), an arachidonic acid metabolite that has been reported to suppress inflammation and cell migration. LXA4 and BML-111, an agonist of the LXA4 receptor/formyl peptide receptor 2 (ALX/FPR2), suppressed microglial activation; LXA4 strongly inhibited the migration of neutrophil-like cells in vitro. ALX/FPR2 was expressed on neutrophils in the ICH mouse brain and the daily administration of BML-111 attenuated the motor coordination dysfunction and suppressed the production of proinflammatory cytokines in the ICH mouse brain. On the other hand, BML-111 did not show a significant reduction in the number of microglia and neutrophils. These results suggest that systemic administration of ALX/FPR2 agonists may suppress the neuroinflammatory response of microglia and neutrophils without a change in cell numbers. Additionally, their combination with molecules that reduce cell numbers, such as modulators of leukotriene B4 signaling, may be required in future studies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.