Möbius Hans J, Stöffler Albrecht, Graham Stephen M
Merz Pharmaceuticals, Frankfurt, Germany.
Drugs Today (Barc). 2004 Aug;40(8):685-95.
Memantine (Axura, Merz Pharmaceuticals GmbH; Ebixa, H. Lundbeck A/S, Namenda, Forest Laboratories, Inc.) is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist with low to moderate affinity for the (+)MK-801 binding site. It is characterized as a voltage-sensitive open-channel NMDA receptor blocker that antagonizes NMDA receptor-mediated inward currents in vitro with an IC50 of 1-3 microM. In animal models, memantine displays both neuroprotective (antiexcitotoxic) and cognition-enhancing properties at therapeutically relevant concentrations. The strong voltage dependency and rapid blocking/unblocking kinetics of memantine are thought to be the basis for its excellent clinical tolerability. Recently completed clinical studies demonstrate positive effects of memantine in Alzheimer's disease both as a monotherapy and in patients receiving continuous donepezil treatment. Memantine treatment also has demonstrated significant improvement of cognitive performance in patients suffering from vascular dementia. Furthermore, the safety and tolerability of memantine in clinical trials has been excellent, with the incidence of premature withdrawals due to adverse events no greater than placebo and overall low frequencies of total adverse events. In 2002, memantine was approved by the European Medicines Agency (EMEA) for the treatment of moderately severe to severe Alzheimer's disease. More recently, memantine was approved in the US for the treatment of moderate to severe Alzheimer's disease (October 2003). Here, we review the most recent pharmacological and clinical data in dementia patients that has emerged from the systematic evaluation of memantine.
美金刚（Axura，默克制药有限公司；Ebixa，H. 伦贝克公司；Namenda，森林实验室公司）是一种非竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，对（+）MK-801结合位点具有低至中等亲和力。它被表征为一种电压敏感性开放通道NMDA受体阻滞剂，在体外以1 - 3微摩尔的半数抑制浓度（IC50）拮抗NMDA受体介导的内向电流。在动物模型中，美金刚在治疗相关浓度下表现出神经保护（抗兴奋毒性）和认知增强特性。美金刚强烈的电压依赖性和快速的阻断/解除阻断动力学被认为是其出色临床耐受性的基础。最近完成的临床研究表明，美金刚作为单一疗法以及在接受持续多奈哌齐治疗的患者中，对阿尔茨海默病均有积极作用。美金刚治疗还在患有血管性痴呆的患者中显示出认知能力的显著改善。此外，美金刚在临床试验中的安全性和耐受性良好，因不良事件导致的提前停药发生率不高于安慰剂，且总体不良事件发生率较低。2002年，美金刚被欧洲药品管理局（EMEA）批准用于治疗中度至重度阿尔茨海默病。最近，美金刚在美国被批准用于治疗中度至重度阿尔茨海默病（2003年10月）。在此，我们回顾了对美金刚进行系统评估后得出的痴呆患者最新药理学和临床数据。
