Pharmacology · Cholinesterase inhibitors
Donepezil !
A once-daily cholinesterase inhibitor for Alzheimer dementia. It modestly helps memory and daily function but does not stop the disease.
Updated 2026-11-01
The figure shows donepezil bound to human acetylcholinesterase; it spans the deep gorge of the enzyme, from the catalytic site to the peripheral site at its mouth.
Mechanism of action
Alzheimer disease destroys acetylcholine-producing neurons that project to the cortex. Donepezil reversibly inhibits acetylcholinesterase in the brain, so the acetylcholine still released lasts longer. This improves cognitive symptoms in some people; there is no evidence that it changes the course of the disease.
- Crosses into the brain
- Binds acetylcholinesterase reversibly along its gorge
- Remaining acetylcholine lasts longer at cortical synapses
- Cognitive symptoms improve modestly
Pharmacokinetics
- Absorption
- Well absorbed by mouth; food does not change it
- Distribution
- About 96% bound to plasma proteins
- Metabolism
- In the liver by CYP2D6 and CYP3A4, and by glucuronidation
- Elimination
- Urine (unchanged drug and metabolites) and faeces
- Half-life
- About 70 hours, which allows one dose a day
Indications
- Dementia of the Alzheimer type, mild, moderate and severe Alzheimer disease →
Adverse effects
Common
- Nausea, diarrhoea, vomiting and loss of appetite
- Insomnia and abnormal dreams
- Muscle cramps and fatigue
- Weight loss
Contraindications
- Hypersensitivity to donepezil or to piperidine derivatives
Key interactions
- Anticholinergic drugs (oxybutynin, tricyclics, first-generation antihistamines)
- Opposite effects: each weakens the other
- Succinylcholine and cholinergic agonists such as bethanechol
- Additive effects; prolonged muscle relaxation in anaesthesia
- NSAIDs
- Higher risk of gastrointestinal bleeding
What is monitored
- Heart rate and any fainting or falls
- Weight and appetite
- Signs of gastrointestinal bleeding
- Cognition and daily function over months
Administration and safety
- Taken once a day, usually in the evening before bedtime
- Higher-strength tablets are swallowed whole
- An anaesthetist is told about it before surgery
Nursing care
- Check pulse; report a slow heart rate, dizziness or fainting
- Watch for nausea, vomiting and weight loss, mainly when starting or increasing the dose
- Ask caregivers about black stools or vomiting blood
- Set realistic expectations with the family: it eases symptoms, it does not cure
Pregnancy and breastfeeding
Not studied in pregnant women; it is used mainly in older adults.
Test yourself
Think of the answer, then tap the question to see it.
Why can donepezil be given once a day?
Its elimination half-life is long, about 70 hours.
Which cardiac effect is a class warning for donepezil and why does it happen?
Bradycardia or heart block, from increased vagal (cholinergic) effect on the sinus and AV nodes.
Does donepezil slow the progression of Alzheimer disease?
No. It improves symptoms in some people but there is no evidence it changes the underlying disease.
Related drugs
Related conditions
← Back to the class: Cholinesterase inhibitors
Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.
Sources: DailyMed - DONEPEZIL HYDROCHLORIDE tablet, film coated (DailyMed (U.S. National Library of Medicine), 2026); Donepezil: MedlinePlus Drug Information (MedlinePlus (U.S. National Library of Medicine), 2026); RCSB PDB - 4EY7: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Donepezil (RCSB Protein Data Bank, 2026); Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th ed., ch. 21 (McGraw Hill, 2023).
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Representative model, for educational purposes only.