Randolph C, Roberts J W, Tierney M C, Bravi D, Mouradian M M, Chase T N
Experimental Therapeutics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland.
Alzheimer Dis Assoc Disord. 1994 Fall;8(3):198-205. doi: 10.1097/00002093-199408030-00006.
Degeneration of cortical glutamatergic projections may contribute to the cognitive decline in Alzheimer disease (AD). To evaluate whether 1glutamate system stimulation might confer symptomatic benefit, we administered D-cycloserine, a putative partial indirect agonist at certain N-methyl-D-aspartate (NMDA) glutamate receptors, to 12 patients with probable AD. The patients (seven men, five women) had a mean age of 65 +/- 8.4 years; Mini Mental State Examination scores ranged from 15 to 25. A dose escalation phase, in which cycloserine was given in daily oral doses from 25 to 500 mg (total of six dose levels, 1 week per dose), was followed by a "best dose" crossover comparison with placebo under double-blind conditions. The crossover phase consisted of 2 weeks of cycloserine and 2 weeks of placebo, separated by a 1-week washout period. We observed no significant or consistent effect on neuropsychological outcome measures. The results suggest that short-term potentiation of NMDA-mediated glutamatergic transmission may not prove useful in the symptomatic treatment of Alzheimer dementia.
皮质谷氨酸能投射的退化可能导致阿尔茨海默病（AD）的认知衰退。为了评估谷氨酸系统刺激是否可能带来症状改善，我们对12例可能患有AD的患者给予了D-环丝氨酸，它是一种假定的某些N-甲基-D-天冬氨酸（NMDA）谷氨酸受体的部分间接激动剂。患者（7名男性，5名女性）平均年龄为65±8.4岁；简易精神状态检查评分在15至25分之间。在剂量递增阶段，环丝氨酸每日口服剂量从25毫克至500毫克（共六个剂量水平，每个剂量1周），随后在双盲条件下与安慰剂进行“最佳剂量”交叉比较。交叉阶段包括2周的环丝氨酸治疗和2周的安慰剂治疗，中间有1周的洗脱期。我们未观察到对神经心理学结果指标有显著或一致的影响。结果表明，NMDA介导的谷氨酸能传递的短期增强可能在阿尔茨海默痴呆的症状治疗中并无用处。
