Reversal of scopolamine‐induced deficits with a single dose of donepezil, an acetylcholinesterase inhibitor

Alzheimer's & Dementia - Tập 1 Số 2 - Trang 126-135 - 2005
Peter J. Snyder1,2, Martin M. Bednar2, Jennifer Cromer1, Paul Maruff3,4
1Department of Psychology, University of Connecticut, 406 Babbidge Road, Unit 1020, Storrs, CT, 06269-1020, USA
2Pfizer Global Research & Development Groton CT USA
3Cogstate Ltd., Melbourne, Australia
4School of Psychological Science LaTrobe University Melbourne Australia

Tóm tắt

BackgroundTo develop a more rapid screening paradigm for novel cognitive enhancers, the authors sought to determine the utility of a well‐known pharmacologic model of induced dementia (scopolamine challenge), paired with a sensitive neuropsychological test, for assessing the ability of a single oral dose of a current treatment for Alzheimer's disease (donepezil) to improve cognitive performance in healthy elderly subjects.MethodsThirty‐two (4 groups of 8) healthy elderly volunteers were put randomly into a double‐blind, placebo‐controlled, modified crossover design study. In Part 1, 16 subjects received donepezil (5 mg) or placebo separately in a crossover fashion. In Part 2, the remaining 2 groups of 8 subjects received scopolamine (0.3 mg subcutaneously) with each group then were assigned randomly to receive donepezil (5 mg) or placebo (in a crossover fashion) 3 hours postbaseline. A novel measure of visuospatial working memory and executive controls, the Groton Maze Learning Test (GMLT), was administered to each subject at baseline and at 2.5, 4, 5.5, 7, and 9 hours after dosing of donepezil.ResultsWith scopolamine, subjects showed slower psychomotor speed, reduced accuracy and learning efficiency, and longer time required to navigate a hidden maze. Concurrent administration of donepezil significantly reversed these deficits and resulted in a faster recovery time. In addition, single doses of donepezil alone led to improved psychomotor speed, accuracy, and learning efficiency.ConclusionsRobust effects of single‐dose donepezil on cognition can be readily observed, with the use of a complex hidden maze learning task, both with and without a scopolamine‐induced deficit model in healthy elderly adults.

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Alzheimer's & Dementia

Tập 1 Số 2

126-135

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