[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/cholinesterase-inhibitors/) › Donepezil

[Pharmacology](https://durgical.com/en/pharmacology/) · [Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/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

- Class: [Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/cholinesterase-inhibitors/)
- Enzyme: Acetylcholinesterase
- ATC code: N06DA02

✂**Acetylcholinesterase**Donepezil

ⓘ 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.

**Target in 3D:** Acetylcholinesterase. PDB structure 4EY7 (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/4EY7) · Drag to rotate · pinch to zoom

## 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 →](https://durgical.com/en/conditions/alzheimer-disease/)

## Adverse effects

### Common

- Nausea, diarrhoea, vomiting and loss of appetite
- Insomnia and abnormal dreams
- Muscle cramps and fatigue
- Weight loss

### Serious (rare, important)

- Bradycardia, heart block and fainting
- Stomach or bowel bleeding, especially with NSAIDs or a past ulcer
- Seizures
- QT prolongation and torsades de pointes (reported after marketing)

## 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.

## Memory aid

DONEpezil is the «once-a-day» one: a long half-life lets a single evening dose do the job.

## 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.

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## Related drugs

- [Rivastigmine](https://durgical.com/en/pharmacology/rivastigmine/)
- [Galantamine](https://durgical.com/en/pharmacology/galantamine/)

## Related conditions

- [Alzheimer disease](https://durgical.com/en/conditions/alzheimer-disease/)

[← Back to the class: Cholinesterase inhibitors](https://durgical.com/en/pharmacology/classes/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](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=12a755c5-1ad9-43d1-832a-eb2ff17bd693) (DailyMed (U.S. National Library of Medicine), 2026); [Donepezil: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a697032.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [RCSB PDB - 4EY7: Crystal Structure of Recombinant Human Acetylcholinesterase in Complex with Donepezil](https://www.rcsb.org/structure/4EY7) (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.

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