Hepatotoxicity limits the clinical utility of the cholinesterase inhibitor 
tacrine as a palliative therapy for Alzheimer's disease. The present studies 
examined the effects of E2020, a selective acetylcholinesterase inhibitor not 
associated with liver toxicity in man, on cognitive performance in rhesus 
monkeys using tasks employed previously to evaluate tacrine and other 
cholinomimetic agents. The ability of E2020 to prevent the induction of a 
cognitive impairment by the muscarinic receptor antagonist scopolamine was 
assessed using an automated spatial delayed response task. Coadministration of 
E2020 (0.5-1.75 mg/kg) caused a dose-dependent reversal of the scopolamine (0.03 
mg/kg) induced impairment observed after retention intervals of 10 and 20 s. At 
the highest dose of E2020 examined (1.75 mg/kg), choice accuracy approached 
normal control levels. In this dose range, E2020 was well tolerated, but at the 
higher dose of 2 mg/kg, cholinergic side-effects were apparent. The effect of 
E2020 on choice accuracy in a visual recognition task was also assessed as this 
task does not require the use of scopolamine to disrupt performance and 
beneficial effects of cholinomimetics can therefore be detected at lower doses 
than in the spatial memory paradigm. In this task, administration of E2020 
increased choice accuracy from 59 +/- 1% correct to up to 71 +/- 2% at doses of 
0.03 and 0.05 mg/kg. No observable adverse effects were induced by E2020 in this 
dose range. The ability of E2020 to improve performance in these cognitive tasks 
resembles the profile of other cholinesterase inhibitors, including tacrine, 
that also improve cognitive function in Alzheimer's disease patients. Because of 
its more favourable clinical safety profile, E2020 may provide a significantly 
improved palliative therapy for dementia.