Cholinesterase Inhibitors in Dementia

Donepezil is the number one member of the second generation of acetylcholinesterase inhibitors (AChEIs) (i.e., donepezil, rivastigmine, galantamine) developed for the treatment of Alzheimer’s disease after the postulation in the early 1980s that AD was associated with a central cholinergic deficit. The first generation of AChEIs was represented by physostigmine, tacrine, velnacrine and metrifonate of which only tacrine reached the market in 1993 with an ephemeral life due to pharmacokinetic and pharmacodynamic problems. After the shut down of the tacrine business, donepezil became the new star of AD therapeutics from 1996 up to now. More than 1000 papers have been published on the properties of donepezil during the past decade (1996-2006). About 800 papers deal with donepezil in dementia (>300 clinical trials worldwide), and approximately 100 papers refer to the role of donepezil in other CNS disorders.



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