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

• Published in: Neuroscience letters 2023-07, Vol.810, p.137332-137332, Article 137332
• Main Authors: Abolhasani, Fatemeh, Pourshojaei, Yaghoub, Mohammadi, Fatemeh, Esmaeilpour, Khadijeh, Asadipour, Ali, Ilaghi, Mehran, Shabani, Mohammad
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Cholinesterase inhibitor; Compound 7c; Phenoxyethyl piperidine derivative
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2023.137332

[Display omitted] •STZ model of dementia exhibited elevated levels of acetylcholinesterase (AChE), as well as impaired passive avoidance memory.•Compound 7c, a phenoxyethyl piperidine derivative, decreased the hippocampal AChE and ameliorated the memory impairment.•Phenoxyethyl piperidine derivatives with cholinesterase inhibitory properties might be promising agents in treating dementia. 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.