The discovery of acetylcholine and acetylcholinesterase provided the first insight into the intricacies of chemical signal transduction and neuronal communication. Further elucidation of the underlying mechanisms led to an attendant leveraging of this knowledge via the synthesis of new therapeutics designed to control aberrant biochemical processes. The central role of the cholinergic system within human memory and learning, as well as its implication in Alzheimer's disease, has made it a point of focus within the neuropharmacology and medicinal chemistry communities. This review is focused on donepezil and covers the background, synthetic routes, structure-activity relationships, binding interactions with acetylcholinesterase, pharmacokinetics and metabolism, efficacy, adverse effects, and historical importance of this leading therapeutic in the treatment of Alzheimer's disease and true Classic in Chemical Neuroscience.
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