Molinuevo José L, Lladó Albert, Rami Lorena
Unitat Memoria-Alzheimer, Institut Clinic Malalties del Sistema Nerviós, Hospital Clinic i Universitari, Barcelona, Spain.
Am J Alzheimers Dis Other Demen. 2005 Mar-Apr;20(2):77-85. doi: 10.1177/153331750502000206.
The management of dementia has changed since the development of new antidementia drugs. The benefits observed in Alzheimer's disease (AD) with selective cholinergic transmission treatments are mainly symptomatic, without clear evidence of neuroprotection. The hypothesis that glutamate-mediated neurotoxicity is involved in the pathogenesis of AD is finding increasingly more acceptance in the scientific community. Glutamate receptors are overactive, and N-methyl-D-aspartate (NMDA) receptor antagonists have therapeutic potential for the treatment of AD and other neurological disorders. Memantine is a noncompetitive NMDA antagonist that is considered a neuroprotective drug. Memantine's capacity has been demonstrated in preclinical studies, and it is considered a useful symptomatic treatment for AD. Memantine has been shown to benefit cognition, function, and global outcome in patients with moderate to severe AD, and it is currently approved by the US Food and Drug Administration (FDA) for the treatment of moderate to severe AD. Recently, memantine has also demonstrated efficacy in the initial stages of AD, although FDA authorization is pending. This review highlights the important pharmacological and clinical aspects of memantine, as well as some basic mechanisms mediating glutamatergic neurodegeneration.
自从新型抗痴呆药物研发以来，痴呆症的治疗方式发生了变化。在阿尔茨海默病（AD）中，选择性胆碱能传递治疗所观察到的益处主要是对症治疗，没有明确的神经保护证据。谷氨酸介导的神经毒性参与AD发病机制这一假说在科学界越来越被接受。谷氨酸受体过度活跃，N-甲基-D-天冬氨酸（NMDA）受体拮抗剂对AD及其他神经疾病具有治疗潜力。美金刚是一种非竞争性NMDA拮抗剂，被认为是一种神经保护药物。美金刚的能力已在临床前研究中得到证实，它被认为是一种有效的AD对症治疗药物。美金刚已被证明可使中度至重度AD患者的认知、功能及整体预后受益，目前已被美国食品药品监督管理局（FDA）批准用于治疗中度至重度AD。最近，美金刚在AD的初始阶段也显示出疗效，不过FDA的批准尚在等待中。本综述重点介绍了美金刚重要的药理学和临床方面，以及一些介导谷氨酸能神经变性的基本机制。
