Minkeviciene Rimante, Banerjee Pradeep, Tanila Heikki
Department of Neurobiology, A.I.Virtanen Institute for Molecular sciences, University of Kuopio, Kuopio, Finland.
Neuropharmacology. 2008 Jun;54(7):1079-85. doi: 10.1016/j.neuropharm.2008.02.014. Epub 2008 Feb 29.
Memantine, a moderate-affinity NMDA receptor antagonist, is clinically used for the treatment of Alzheimer's disease (AD). Both clinical and preclinical studies have shown that memantine, at doses producing a steady-state plasma level of 0.5-1 microM, is well tolerated and improves cognition. Here we tested the effects of chronic oral administration of memantine (10, 30 and 100mg/kg per day) producing steady state plasma drug levels ranging between approximately 0.5 and 6 microM on motor, social, emotional and cognitive behavior in normal C57BL/6J mice. Memantine dose-dependently reduced escape latency (hidden platform) and decreased wall swimming tendency in the Morris water maze test, increased time spent in open arms in the elevated plus-maze test, and reduced the number of isolation-induced aggressive attacks, but did not affect exploratory activity in the open field. These data indicate that high, stable doses of memantine improved cognition and exhibited a potential anxiolytic response in normal mice.
美金刚是一种中等亲和力的N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，临床上用于治疗阿尔茨海默病（AD）。临床和临床前研究均表明，美金刚在产生0.5 - 1微摩尔稳态血浆水平的剂量下，耐受性良好且能改善认知。在此，我们测试了在正常C57BL/6J小鼠中，慢性口服美金刚（每天10、30和100毫克/千克）产生约0.5至6微摩尔稳态血浆药物水平对运动、社交、情感和认知行为的影响。在莫里斯水迷宫试验中，美金刚剂量依赖性地缩短了逃避潜伏期（隐藏平台）并降低了壁泳倾向，在高架十字迷宫试验中增加了在开放臂的停留时间，并减少了隔离诱导的攻击次数，但不影响旷场试验中的探索活动。这些数据表明，高剂量、稳定剂量的美金刚可改善正常小鼠的认知并表现出潜在的抗焦虑反应。
