Farlow Martin R
Department of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Geriatrics. 2004 Jun;59(6):22-7.
Research into Alzheimer's disease (AD) pathology has identified several underlying disease processes that are potential targets for drug discovery and development. One strategy targets glutamatergic neurotransmission mediated by the N-methyl-D-aspartate (NMDA) receptor. Therapeutic intervention with high-affinity NMDA receptor antagonists, such as phencyclidine (PCP) and MK-801, is not practical due to adverse side effects; however, a low-moderate affinity, uncompetitive and strongly voltage-dependent NMDA receptor antagonist, memantine (NamendaTM), is well tolerated and recently has been approved by the U.S. Food and Drug Administration for the treatment of moderate to severe AD. Clinical results support NMDA receptor antagonism as a viable therapeutic strategy for AD and suggest that this novel pharmacologic approach, either alone or in combination with other drugs, is likely to significantly impact the current AD treatment paradigm.
对阿尔茨海默病（AD）病理学的研究已经确定了几种潜在的疾病进程，这些进程是药物发现和开发的潜在靶点。一种策略针对由N-甲基-D-天冬氨酸（NMDA）受体介导的谷氨酸能神经传递。使用高亲和力的NMDA受体拮抗剂进行治疗干预，如苯环己哌啶（PCP）和MK-801，由于副作用而不实用；然而，一种低至中等亲和力、非竞争性且强烈电压依赖性的NMDA受体拮抗剂美金刚（NamendaTM）耐受性良好，最近已被美国食品药品监督管理局批准用于治疗中度至重度AD。临床结果支持NMDA受体拮抗作用作为AD的一种可行治疗策略，并表明这种新的药理学方法，无论是单独使用还是与其他药物联合使用，都可能对当前的AD治疗模式产生重大影响。
