Möbius Hans J
Merz Pharmaceuticals, Frankfurt/M, Germany.
Int J Geriatr Psychiatry. 2003 Sep;18(Suppl 1):S47-54. doi: 10.1002/gps.939.
Nine years after the initial approval of a cholinergic drug for the treatment of Alzheimer's Disease in the USA, a compound with a different pharmacological approach, namely the NMDA antagonist memantine, has been approved for the first time in Europe in 2002. This event led to an enhanced perception of a decade of basic research work on its mode of action. At the same time, additional preclinical data, e.g. on memantine's effects on the hyperphosphorylation of tau, and clinical trial results, e.g. on the glutamatergic-cholinergic combination therapy, are being reported. The present paper attempts to provide an update on the currently available pharmacological and clinical evidence on memantine, including earlier clincial data, e.g. in vascular dementia. As the clinical database broadens, and various additional conditions are being tested in ongoing controlled clinical trials, we are approaching an ever more precise profile of memantine's spectrum of safety and tolerability, and also varied efficacy-hopefully resulting in another useful tool in the clinician's hands to fight previously untreatable neurodegenerative disease.
在美国首次批准一种用于治疗阿尔茨海默病的胆碱能药物九年后，一种采用不同药理学方法的化合物，即N-甲基-D-天冬氨酸（NMDA）拮抗剂美金刚，于2002年在欧洲首次获批。这一事件使人们对关于其作用方式的十年基础研究工作有了更强的认识。与此同时，更多的临床前数据，如美金刚对tau蛋白过度磷酸化的影响，以及临床试验结果，如谷氨酸能-胆碱能联合疗法的结果，也不断被报道。本文试图提供关于美金刚目前可用的药理学和临床证据的最新情况，包括早期的临床数据，如在血管性痴呆方面的数据。随着临床数据库的扩大，并且在正在进行的对照临床试验中对各种其他病症进行测试，我们正在逐渐获得关于美金刚安全性和耐受性范围以及不同疗效的更精确描述——有望为临床医生提供另一种有用的工具来对抗以前无法治疗的神经退行性疾病。
