Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:
Open accessAbstract
Background Cholinesterase (ChE) inhibitors currently used in the treatment of Alzheimer's disease (AD) are the acetylcholinesterase (AChE)-selective inhibitors, donepezil and galantamine, and the dual AChE and butyrylcholinesterase (BuChE) inhibitor, rivastigmine. In addition to differences in selectivity for AChE and BuChE, ChE inhibitors also differ in pharmacokinetic and pharmacodynamic properties, and these differences could significantly impact on safety, tolerability, and efficacy.Objective The aim of this article was to provide an overview of the ChE inhibitors widely used in AD, focusing on key pharmacologic differences among agents and how these may translate into important differences in safety, tolerability, and efficacy in clinical practice.Methods Using published literature collected over time by the author, a review was conducted, focusing on the pharmacology and clinical data of donepezil, galantamine, and rivastigmine.Results All ChE inhibitors have the potential to induce centrally mediated cholinergic adverse events (AEs), such as nausea and vomiting, if the dose is increased too rapidly or in increments that are too large. These AEs, which are most likely to occur during the "getting on," or dose-escalation, phase of treatment, may result in patients discontinuing treatment early without achieving optimum therapeutic benefit. To reduce the incidence of these AEs, a slow dose-escalation schedule has been established in clinical practice, consisting of a "start low, go slow" procedure with a minimum of 4 weeks between dose increases. After "getting on" treatment, maintaining treatment in the long term, or "staying on," may be achieved with good safety, tolerability, and sustained symptomatic efficacy across the key symptom domains (activities of daily living, behavior, and cognition).Conclusions ChE inhibitors provide symptomatic benefit in AD across key symptom domains. Factors influencing the safety, tolerability, and efficacy of these agents in clinical practice include ChE enzymes inhibited, brain and brain-region ChE selectivity, and metabolism route. Class-specific cholinergic AEs can be minimized using slow, flexible dose escalation.
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Rivastigmine can hydrolyze butyrylcholinesterase present at glial cells of the temporal cortex region of the brain.
“Rivastigmine can also hydrolyze the butyrylcholinesterase (BuChE) present at glial cells of the temporal cortex region of the brain [33].”
From Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy (2021) · cites this paper as [33]
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- Authors
- Grossberg, G. T.
- Affiliations
- Saint Louis University (US)
- Corresponding author
- Grossberg, George T
- ORCID
- Grossberg, George T
- Venue
- Current Therapeutic Research
- Publisher
- Elsevier BV
- Published
- 2003-04
- Volume
- 64
- Issue
- 4
- Pages
- 216-235
- ISSN
- 0011-393X (ISSN-L)
- PMC
- PMC4052996
- OpenAlex
- W170237590
- Cited by
- 384
- References
- 101
- Citations by year
- 2026: 26 · 2025: 45 · 2024: 72 · 2023: 41 · 2022: 28 · 2021: 27 · 2020: 20 · 2019: 24 · 2018: 19 · 2017: 14 · 2016: 11 · 2015: 7 · 2014: 3 · 2013: 7 · 2012: 5
- FWCI
- 3.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Current Therapeutic Research (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Novartis Pharma
- Topics
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Physiology › 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, galantamine, rivastigmine, acetylcholinesterase inhibitors, butyrylcholinesterase inhibitors, dose escalation, safety and tolerability
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