Therapeutic efficacy of novel memantine nitrate MN-08 in animal models of Alzheimer′s disease and vascular dementia
作者机构：Institute of New Drug Research College of Pharmacy Jinan University State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences University of Macau
出 版 物：《中国药理学与毒理学杂志》 (Chinese Journal of Pharmacology and Toxicology)
年 卷 期：2023年第37卷第7期
页 面：492-493页
学科分类：1002[医学-临床医学] 100205[医学-精神病与精神卫生学] 10[医学]
基 金：National Natural Science Foundation of China (82061160374) Science and Technology Development Fund,Macau SAR (0035/2020/AGJ)
摘 要：OBJECTIVE Alzheimer′s disease (AD)and vascular dementia (VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are *** of N-methylD-aspartate (NMDA) receptors,decreased cerebral blood flow,and subsequent pathological events,play significant roles in the progression of AD and *** In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with *** MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice (following a 6-month preventative course) and in 8-month-old triple-transgenic (3×Tg-AD) mice (following a4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic *** vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregulations of the ERK and PI3K/Akt/GSK3β pathway,subsequently preventing glutamate-induced neuronal ***,MN-08 exhibited favorable pharmacokinetics,blood-brain barrier penetration,and safety profiles in rats and beagle *** These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.
同方期刊数据库