Exploring the potential of a novel phenoxyethyl piperidine derivative with cholinesterase inhibitory properties as a treatment for dementia: Insights from STZ animal model of dementia

乙酰胆碱酯酶 海马体 莫里斯水上航行任务 痴呆 丁酰胆碱酯酶 多奈哌齐 阿切 胆碱酯酶 记忆障碍 链脲佐菌素 药理学 心理学 神经科学 阿尔茨海默病 海马结构 医学 内科学 认知 内分泌学 化学 疾病 糖尿病 生物化学
作者
F Abolhasani,Yaghoub Pourshojaei,Fatemeh Mohammadi,Khadijeh Esmaeilpour,Ali Asadipour,Mehran Ilaghi,Mohammad Shabani
出处
期刊:Neuroscience Letters [Elsevier]
卷期号:810: 137332-137332
标识
DOI:10.1016/j.neulet.2023.137332
摘要

Alzheimer's disease (AD) is a neurodegenerative disease, often characterized by progressive deficits in memory and cognitive functions. Cholinesterase inhibitors have been introduced as promising agents to enhance cognition and memory in both human patients and animal models of AD. In the current study, we assessed the effects of a synthetic phenoxyethyl piperidine derivative, compound 7c, as a novel dual inhibitor of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE), on learning and memory, as well as serum and hippocampal AChE levels in an animal model of AD. The model of dementia was induced by intracerebroventricular injection of streptozotocin (STZ, 2 mg/kg) to male Wistar rats. STZ-treated rats received compound 7c (3, 30, and 300 µg/kg) for five consecutive days. ​Passive avoidance (PA) learning and memory, as well as spatial learning and memory using Morris water maze, were evaluated. The level of AChE was measured in the serum and the left and right hippocampus. Findings demonstrated that compound 7c (300 µg/kg) was able to reverse STZ-induced impairments in PA memory, while also reduced the increased AChE level in the left hippocampus. Taken together, compound 7c appeared to act as a central AChE inhibitor, and its role in alleviating cognitive deficits in the AD animal model suggests that it may have therapeutic potential in AD dementia. Further research is required to assess the effectiveness of compound 7c in more reliable models of AD in light of these preliminary findings.

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