Cited by 231Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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Cholinesterase Inhibitors and Beyond

Pepeu, Giancarlo, Giovannini, Maria·2009·Current Alzheimer Research

DOI 10.2174/156720509787602861

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Abstract

Cholinesterase inhibitors (ChEIs) were introduced in the therapy of Alzheimer Disease (AD) in the nineteen nineties with great expectations. The hopes and large interest raised by these drugs are well demonstrated by 12,000 references listed by PubMed under 'ChEI' for 1995-2007. The list is reduced to 2500 if we confine ourselves to 'ChEIs and dementia'. Of them, about 500 were published in the last two years. Whereas an increase in brain acetylcholine and an improvement of cognitive deficits have been consistently demonstrated in animal models of AD, from aging rats to transgenic mice, the clinical effectiveness of ChEIs has been and is still a matter of contrasting opinions. These range from the negative conclusions of the AD2000 trial on donepezil, claiming that it is not cost effective, with benefits below a minimally relevant threshold, to the NICE appraisal of 2007 declaring that donepezil, rivastigmine, galantamine are efficacious for mild to moderate AD, irrespective of their different selectivity for acetyl- (AChE) and butyrylcholinesterase (BuChE). The possibility that ChEIs may exert their effects through mechanisms beyond cholinesterase inhibition has been envisaged. However, according to the information presented in this review, the "classical" ChEIs, donepezil, rivastigmine and galantamine, show no pharmacological actions beyond cholinesterase inhibition which may play an important role in their therapeutic efficacy. The diverging opinions on clinical efficacy do not discourage from developing new ChEIs, and particularly the so called multifunctional ChEIs. They represent the future of the cholinergic therapy for AD but other indications for these drugs may be considered, including vascular dementia, mild cognitive impairment, and the ethically sensitive improvement of memory and learning in healthy subjects.

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Authors: Pepeu, G., & Giovannini, M.
Affiliations: University of Florence (IT)
Corresponding author: Giovannini, Maria
ORCID: Giovannini, Maria
Venue: Current Alzheimer Research
Publisher: Bentham Science Publishers Ltd.
Published: 2009-04-01
Volume: 6
Issue: 2
Pages: 86-96
ISSN: 1567-2050 (ISSN-L)
DOI: 10.2174/156720509787602861
OpenAlex: W2133779850
Cited by: 209
References: 96
Citations by year: 2026: 3 · 2025: 6 · 2024: 9 · 2023: 7 · 2022: 10 · 2021: 1 · 2020: 12 · 2019: 13 · 2018: 8 · 2017: 8 · 2016: 15 · 2015: 19 · 2014: 22 · 2013: 12 · 2012: 19
FWCI: 15.57
Type: journal article
Language: en
Open access: closed
Locations: Current Alzheimer Research (publishedVersion)
PubMed (publishedVersion)
Florence Research (University of Florence) (submittedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: cholinesterase inhibitors, Alzheimer's disease, donepezil, rivastigmine, galantamine, acetylcholinesterase, butyrylcholinesterase, cholinergic therapy, vascular dementia, mild cognitive impairment, memory enhancement, clinical efficacy
MeSH terms: Acetylcholine, Alzheimer Disease, Animals, Brain, Cholinesterase Inhibitors, Cholinesterases, Clinical Trials as Topic, Cognition Disorders, Humans, Antipsychotic Agents, History, 20th Century, History, 21st Century

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