The recovery of cerebrospinal fluid acetylcholinesterase activity in Alzheimer's disease patients after treatment with metrifonate

We investigated the relationship between peripheral and central cholinester ase (ChE) inhibition levels after chronic treatment of Alzheimer's disease (AD) patients with metrifonate (MTF). In a 6-month, double-blind, placebo-c ontrolled 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) acetylcholines terase (AChE) and plasma butyrylcholinesterase (BuChE), respectively. In an other study, AD patients were treated with daily MTF to achieve RBC AChE in hibition 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. T hese 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 d ata do not support continous central neuronal AChE inhibition as the mechan ism for the long-term efficacy of metrifonate for the treatment of AD. (C) 2000 Prous Science. All rights reserved.