EFFECTS OF METRIFONATE, A LONG-ACTING CHOLINESTERASE INHIBITOR, IN ALZHEIMER-DISEASE - REPORT OF AN OPEN TRIAL
EFFECTS OF METRIFONATE, A LONG-ACTING CHOLINESTERASE INHIBITOR, IN ALZHEIMER-DISEASE - REPORT OF AN OPEN TRIAL
复制标题
DOI：
10.1002/ddr.430190407
复制
发表时间：
1990-01-01
影响因子：
3.8
通讯作者：
ZEC, RF
中科院分区：
文献类型：
--
作者：
BECKER, RE;COLLIVER, J;ZEC, RF
这是第一项对长期在人体内进行的长效胆碱酯酶（ChE）抑制剂美曲磷酯（Met）多次给药试验的研究。我们对20例符合NINCDS-ADRDA标准的可能的阿尔茨海默病（AD）患者进行了Met治疗。在开放条件下，给予患者单次口服剂量的Met，2.5、5、7.5和15 mg/kg/wk。在5 mg/kg/周剂量下观察到阿尔茨海默病评估量表（ADAS）评分的统计学显著性改善。ADAS的最大改善与平均55.9%（±）相关。12.6%标准差）的红细胞（RBC）乙酰胆碱酯酶（AChE）活性水平。超过80%的血浆和红细胞胆碱酯酶的抑制实现只有轻微的副作用。在第二次5 mg/kg/wk Met给药后24小时，2例患者CSF中的胆碱酯酶抑制率分别为37%和47.5%，与第一次给药间隔7天。报告了27例轻微副作用：2.5 mg组无，5 mg组5例，7.5 mg组9例，15 mg组13例。所有副作用均无临床显著性或药物相关性或需要终止治疗或调整剂量。我们的结论是，Met是中枢神经系统胆碱能功能的一种有用的新药理学探针，并且有必要对Met在AD中进行双盲评估。
This is the first study of a multiple-dose trial of metrifonate (Met), a long-acting cholinesterase (ChE) inhibitor, conducted over a prolonged period of time in humans. We have administered Met to 20 patients who met NINCDS-ADRDA criteria for probable Alzheimer disease (AD). Patients were given, under open conditions, single oral doses of Met, 2.5, 5, 7.5, and 15 mg/kg/wk. A statistically significant improvement in the Alzheimer Disease Assessment Scale (ADAS) scores was observed with the 5 mg/kg/wk dose. Maximal improvement on the ADAS was associated with a mean 55.9% (.+-. 12.6% standard deviation) activity level of red blood cell (RBC) acetylcholinesterase (AChE). Over 80% inhibition of plasma and RBC ChE was achieved with only minor side effects. Cholinesterate inhibition in the CSF of two patients was 37% and 47.5% 24 hr after a second dose of 5 mg/kg/wk of Met separated by 7 days from the first dose. Twenty-seven minor side effects were reported: none on 2.5 mg, 5 on 5 mg, 9 on 7.5 mg, and 13 on the 15 mg dose. None of the side effects was clinically significant or drug related or required termination of treatment or dosage adjustment. We conclude that Met is a useful new pharmacological probe of cholinergic function in the central nervous system and that a double-blind evaluation of Met in AD is warranted.