Mohr E, Knott V, Sampson M, Wesnes K, Herting R, Mendis T
Institute of Mental Health Research, Royal Ottawa Hospital/University of Ottawa, Ontario, Canada.
Clin Neuropharmacol. 1995 Feb;18(1):28-38. doi: 10.1097/00002826-199502000-00004.
Cycloserine acts as a potent and selective modulator of the N-methyl-D- aspartate (NMDA) receptor-associated glycine recognition site, which may be a possible mechanism for this compound's positive effects on memory formation and retrieval processes in animals. Studies in normal human volunteers have shown that cycloserine can have significant positive effects on cognitive processing in the elderly and can ameliorate memory deficits induced by subcutaneously administered scopolamine. Based on this profile, a double-blind, placebo controlled, parallel group (three drug dosages) study was conducted as part of a larger study to assess the efficacy and safety, as well as the cognitive and central nervous system (CNS) impact, of 6 months of cycloserine treatment in patients (N = 40) with probable dementia of the Alzheimer type (DAT). The Cognitive Drug Research Computerize Assessment System (CDR System) served as the primary outcome measure of efficacy. CNS activity was assessed using quantified electroencephalography (QEEG). Safety measures included adverse effects documentation and analysis of blood chemistry/hematology. Cycloserine proved to be a safe agent in this population at the doses given but failed to show any statistically significant effects in the areas of cognition and global clinical ratings and did not indicate significant CNS activity on QEEG. These findings suggest that cycloserine has no measurable therapeutic effect on Alzheimer's disease at the doses given.
环丝氨酸可作为N-甲基-D-天冬氨酸（NMDA）受体相关甘氨酸识别位点的有效且选择性调节剂，这可能是该化合物对动物记忆形成和提取过程产生积极作用的一种潜在机制。对正常人类志愿者的研究表明，环丝氨酸对老年人的认知加工可产生显著的积极影响，并可改善皮下注射东莨菪碱所致的记忆缺陷。基于此情况，作为一项更大规模研究的一部分，开展了一项双盲、安慰剂对照、平行组（三种药物剂量）研究，以评估环丝氨酸治疗6个月对40例可能患有阿尔茨海默型痴呆（DAT）患者的疗效和安全性，以及对认知和中枢神经系统（CNS）的影响。认知药物研究计算机评估系统（CDR系统）用作疗效的主要评估指标。使用定量脑电图（QEEG）评估CNS活性。安全措施包括记录不良反应并分析血液化学/血液学指标。在所给剂量下，环丝氨酸在该人群中被证明是一种安全药物，但在认知和整体临床评分方面未显示出任何统计学上的显著效果，并且在QEEG上也未显示出显著的CNS活性。这些发现表明，在所给剂量下，环丝氨酸对阿尔茨海默病没有可测量的治疗效果。
