Verhagen Metman L, Blanchet P J, van den Munckhof P, Del Dotto P, Natté R, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Diseases and Stroke, National Institutes of Health, Bethesda, Maryland 20892-1406, USA.
Mov Disord. 1998 May;13(3):414-7. doi: 10.1002/mds.870130307.
The effects of the NMDA antagonist dextromethorphan (DM) on levodopa-associated dyskinesias and motor fluctuations were studied in patients with advanced Parkinson's disease. During initial open-label dose escalation, 6 of 18 patients reported a beneficial effect at their individually determined optimal DM dose (range, 60-120 mg/day). The 12 remaining patients either experienced reversible side effects, particularly mild drowsiness, or decreased levodopa efficacy, and were therefore excluded from the study. The six responders entered the double-blind, placebo-controlled, crossover study with two 2-week arms separated by 1 week wash-out. On the last day of each arm, motor ratings were performed every 20 minutes for 8 consecutive hours. In addition, motor complications and Activities of Daily Living (ADL) were assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and patient diaries. With DM, dyskinesias improved by 25% according to physician's ratings and by 40% according to UPDRS interviews, without compromising the anti-Parkinson effect of levodopa. Motor fluctuations and ADL scores also improved significantly. Although the narrow therapeutic index of DM limits its clinical usefulness, these findings support the view that drugs acting to inhibit glutamatergic transmission at the NMDA receptor can ameliorate levodopa-associated motor complications.
在晚期帕金森病患者中研究了N-甲基-D-天冬氨酸（NMDA）拮抗剂右美沙芬（DM）对左旋多巴相关异动症和运动波动的影响。在初始开放标签剂量递增期间，18名患者中有6名报告在各自确定的最佳DM剂量（范围为60 - 120毫克/天）时出现有益效果。其余12名患者要么经历了可逆的副作用，尤其是轻度嗜睡，要么左旋多巴疗效降低，因此被排除在研究之外。6名有反应者进入双盲、安慰剂对照的交叉研究，该研究有两个为期2周的阶段，中间间隔1周的洗脱期。在每个阶段的最后一天，连续8小时每20分钟进行一次运动评分。此外，使用统一帕金森病评定量表（UPDRS）和患者日记评估运动并发症和日常生活活动（ADL）。使用DM时，根据医生的评分，异动症改善了25%，根据UPDRS访谈改善了40%，且未损害左旋多巴的抗帕金森病效果。运动波动和ADL评分也显著改善。尽管DM狭窄的治疗指数限制了其临床应用，但这些发现支持这样一种观点，即作用于抑制NMDA受体处谷氨酸能传递的药物可以改善左旋多巴相关的运动并发症。
