Ferris Steven H
Alzheimer's Disease Center, Silberstein Institute for Ageing and Dementia, New York University School of Medicine, 550 First Avenue, Room MHL 310, New York, NY 10016, USA.
Expert Opin Pharmacother. 2003 Dec;4(12):2305-13. doi: 10.1517/14656566.4.12.2305.
Increasing evidence suggests that disturbances in glutamatergic activity play an important role in Alzheimer's disease (AD). Excessive glutamate-mediated activation of NMDA receptors, for example, may contribute to the neuronal death that characterises AD. On the other hand, physiological activation of the NMDA receptor appears necessary for normal cognitive function. Therefore, compounds that finely modulate NMDA receptor activity hold promise as treatments for AD. Memantine (Namenda, Axura, Ebixa; Forest Laboratories, Inc., Merz Pharmaceuticals GmbH, H. Lundbeck A/S) is a low-moderate affinity, uncompetitive NMDA-receptor antagonist that appears to block pathological, but not physiological, activation of the NMDA receptor. Consequently, therapeutic doses of the drug are well-tolerated and do not seem to interfere with the acquisition or processing of cognitive information. Memantine has been shown to improve symptoms and reduce the rate of clinical deterioration among patients with moderate-to-severe AD and was approved in the US for this indication in October 2003. This review provides a brief rationale for the development of memantine as a therapy for AD, as well as an overview of the pharmacology, clinical efficacy, safety and tolerability of this novel therapeutic agent.
越来越多的证据表明，谷氨酸能活性紊乱在阿尔茨海默病（AD）中起重要作用。例如，谷氨酸介导的NMDA受体过度激活可能导致AD特有的神经元死亡。另一方面，NMDA受体的生理激活似乎是正常认知功能所必需的。因此，能够精细调节NMDA受体活性的化合物有望成为治疗AD的药物。美金刚（Namenda、Axura、Ebixa；Forest Laboratories公司、Merz Pharmaceuticals GmbH公司、H. Lundbeck A/S公司）是一种低至中等亲和力的非竞争性NMDA受体拮抗剂，它似乎能阻断NMDA受体的病理性激活，但不影响其生理性激活。因此，该药物的治疗剂量耐受性良好，似乎不会干扰认知信息的获取或处理。美金刚已被证明可改善中度至重度AD患者的症状，并降低临床恶化率，于2003年10月在美国获批用于该适应症。本综述简要阐述了美金刚作为AD治疗药物的研发原理，并概述了这种新型治疗药物的药理学、临床疗效、安全性和耐受性。
