Acute cognitive effects of donepezil in young, healthy volunteers

Objective: The acute nootropic potential of donepezil in young healthy volunteers has not been adequately investigated mainly because in previous studies: (1) effects were assessed before peak-plasma concentration (Tmax) was reached; (2) only a few cognitive processes were assessed. Here we investigated a myriad of cognitive effects of augmentation of acetylcholine using an acute dose of donepezil in healthy adults at theoretical Tmax. Methods: This was a double-blind, placebo controlled, parallel group design study of cognitive effects of acute oral donepezil (5 mg). Subjects were tested twice after donepezil ingestion: 90 min (time that coincides with previous testing in the literature) and 210 min. (theoretical Tmax). The test battery included tasks that tap cognitive domains that are sensitive to acetylcholine manipulations. Results: At both testing times donepezil improved long-term recall of prose, objects recall, recall of spatial locations, and integration of objects with their locations, some effects having been related to self-reported mood enhancement. However, improvement of performance in the central executive measure (backward digit span) occurred only at Tmax. Conclusion: Positive cognitive effects of acute donepezil can be observed in various cognitive domains including mood, but its full nootropic potential is more clearly found close to theoretical peak-plasma concentration. Copyright © 2009 John Wiley & Sons, Ltd.