Unni L, Vicari S, Moriearty P, Schaefer F, Becker R
Department of Psychiatry, Southern Illinois University School of Medicine, Springfield, USA.
Methods Find Exp Clin Pharmacol. 2000 Jan-Feb;22(1):57-61. doi: 10.1358/mf.2000.22.1.795849.
We investigated the relationship between peripheral and central cholinesterase (ChE) inhibition levels after chronic treatment of Alzheimer's disease (AD) patients with metrifonate (MTF). In a 6-month, double-blind, placebo-controlled trial in AD patients treated with a weekly 2.9 mg/kg MTF dose, we observed 17.15 +/- 23.43, 66.92 +/- 7.30 and 60.80 +/- 12.20% inhibition (n = 6) of cerebrospinal fluid (CSF) and red blood cell (RBC) acetylcholinesterase (AChE) and plasma butyrylcholinesterase (BuChE), respectively. In another study, AD patients were treated with daily MTF to achieve RBC AChE inhibition levels of 85.90%. The CSF AChE inhibition was 67.93 +/- 13.69% (n = 3) at 3-4 h after the last treatment and 6.62 +/- 9.36% (n = 2) at 8 days after dosing. The recovery half time of CSF AChE was 2.21 +/- 1.22 days. These data show that CSF AChE recovers faster than the peripheral plasma and RBC enzymes. Under conditions of chronic weekly dosing with MTF, RBC AChE inhibition does not reflect CSF, and arguably, brain AChE inhibition. Our data do not support continuous central neuronal AChE inhibition as the mechanism for the long-term efficacy of metrifonate for the treatment of AD.
我们研究了用敌百虫（MTF）长期治疗阿尔茨海默病（AD）患者后外周和中枢胆碱酯酶（ChE）抑制水平之间的关系。在一项为期6个月的双盲、安慰剂对照试验中，对AD患者每周给予2.9mg/kg的MTF剂量，我们观察到脑脊液（CSF）、红细胞（RBC）乙酰胆碱酯酶（AChE）和血浆丁酰胆碱酯酶（BuChE）的抑制率分别为17.15±23.43%、66.92±7.30%和60.80±12.20%（n = 6）。在另一项研究中，AD患者每日接受MTF治疗，以使RBC AChE抑制水平达到85.90%。末次治疗后3 - 4小时，CSF AChE抑制率为67.93±13.69%（n = 3），给药后8天为6.62±9.36%（n = 2）。CSF AChE的恢复半衰期为2.21±1.22天。这些数据表明，CSF AChE的恢复速度比外周血浆和RBC中的酶更快。在每周给予MTF进行长期给药的情况下，RBC AChE抑制不能反映CSF，也可以说不能反映脑AChE抑制情况。我们的数据不支持持续的中枢神经元AChE抑制作为敌百虫治疗AD长期疗效的机制。
