Schwartz A S, Kohlstaedt E V
Life Sci. 1986 Mar 17;38(11):1021-8. doi: 10.1016/0024-3205(86)90236-5.
Eleven demented patients were administered .004, .009, and .013 mg/kg physostigmine intramuscularly, and placebo, double-blind, in Phase 1. The most effective dose, in terms of showing the best memory score as compared to saline, was repeated during Phase 2. Five patients improved their verbal memory scores in both Phases 1 and 2 after the most effective dose of physostigmine; these five "responders" were found to be significantly more demented than the six "nonresponders." Drug-induced increases in memory scores were significantly correlated with illness severity. Intrusions, which were not a factor in selection of the most effective dose, were reduced in the group as a whole, with the responders showing the most improvement and the nonresponders the least. The association between physostigmine effect and degree of dementia suggests to us that the severe cases may have more permeable blood-brain barriers, and that drug availability to the brain is an important factor in evaluating treatment of SDAT with cholinergic substances.
在第一阶段，对11名痴呆患者进行了双盲、安慰剂对照试验，分别肌肉注射0.004、0.009和0.013毫克/千克的毒扁豆碱。与生理盐水相比，显示出最佳记忆分数的最有效剂量在第二阶段重复使用。五名患者在接受最有效剂量的毒扁豆碱后，在第一阶段和第二阶段的言语记忆分数均有所提高；发现这五名“反应者”的痴呆程度明显高于六名“无反应者”。药物引起的记忆分数增加与疾病严重程度显著相关。在整个组中，侵入性错误（这不是选择最有效剂量的一个因素）有所减少，反应者改善最大，无反应者改善最小。毒扁豆碱效应与痴呆程度之间的关联向我们表明，严重病例的血脑屏障可能更具通透性，并且药物在大脑中的可利用性是评估用胆碱能物质治疗SDAT（老年性痴呆）的一个重要因素。
