Eisen A, Stewart H, Schulzer M, Cameron D
Neuromuscular Diseases Unit, Vancouver General Hospital, British Columbia, Canada.
Can J Neurol Sci. 1993 Nov;20(4):297-301.
Glutamate excitotoxicity is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). We report the results of a double blind, placebo controlled, trial using 100 mg of oral daily lamotrigine (3,5-diamino-6-(2,3 dichlorophenyl)-1,2,4-triazine) which inhibits glutamate release. 67 patients were entered and at trial termination of 1.5 years 15 had withdrawn (9 active and 6 placebo) and 12 had died (6 active and 6 placebo). Mean age at entry was 57.5 years for the active and 58.6 years for the placebo groups. Patients were seen at 3 monthly intervals and scored according to neurological deficit based upon age of onset, bulbar and respiratory involvement, ambulation and functional disability. The mean change in clinical scores for the active versus placebo groups over the trial period was 7.1 +/- 3.3 and 9.0 +/- 3.3 respectively (0.05 < p < 0.10). Changes in cortical threshold and MEP/CMAP ratios to magnetic stimulation also did not differ significantly between the two groups. We conclude that lamotrigine in the doses administered does not alter the course of ALS.
谷氨酸兴奋性毒性与肌萎缩侧索硬化症（ALS）的发病机制有关。我们报告了一项双盲、安慰剂对照试验的结果，该试验使用每日口服100毫克拉莫三嗪（3,5 - 二氨基 - 6 -（2,3 - 二氯苯基）- 1,2,4 - 三嗪），其可抑制谷氨酸释放。共有67名患者入组，在1.5年的试验结束时，有15人退出（9名服用活性药物组和6名服用安慰剂组），12人死亡（6名服用活性药物组和6名服用安慰剂组）。活性药物组入组时的平均年龄为57.5岁，安慰剂组为58.6岁。患者每3个月接受一次检查，并根据发病年龄、延髓和呼吸受累情况、行走能力和功能残疾情况的神经功能缺损进行评分。在试验期间，活性药物组与安慰剂组临床评分的平均变化分别为7.1±3.3和9.0±3.3（0.05 < p < 0.10）。两组之间皮质阈值以及磁刺激的运动诱发电位/复合肌肉动作电位比值的变化也无显著差异。我们得出结论，所给予剂量的拉莫三嗪不会改变ALS的病程。
