DONEPEZIL

Donepezil is a specific and potent acetylcholinesterase inhibitor acco rding to in vitro data. It displays primarily noncompetitive inhibitor y activity. In vivo, donepezil inhibited acetylcholinesterase activity in human erythrocytes and increased extra-cellular acetylcholine leve ls in the cerebral cortex and hippocampus of the rat. Donepezil demons trated efficacy in tests of reference memory in animals, but had less consistent activity in tests of working memory. Donepezil 5 or 10 mg/d ay was associated with significant improvements in cognitive function [assessed by the Alzheimer's Disease Assessment Scale - cognitive subs cale (ADAS-cog)] after 14 and 30 weeks and patient global function (Cl inician's Interview-based Impression of Change incorporating caregiver input score) after 30 weeks, compared with placebo, in patients with mild to moderate Alzheimer's disease. After 2 years, donepezil 5 or 10 mg/day was associated with an ADAS-cog score approximately 4 points b etter than would be expected in untreated patients with mild to modera te Alzheimer's disease. The most common adverse events reported in ass ociation with donepezil 5 mg/day were gastrointestinal events (nausea/ vomiting, diarrhoea, gastric upset and constipation) and dizziness. No hepato-toxicity was reported after 12 weeks' treatment.