Donepezil (Aricept)

Raw research findings for this medication. Mostly single studies, not curated or confirmed robust.

About Donepezil

What it is

Donepezil is a cholinesterase inhibitor: it slows the breakdown of acetylcholine, a messenger important for memory and attention, so more of it stays available in the brain. It is used to ease the symptoms of mild to severe Alzheimer's dementia; it does not stop the underlying disease. It is sold as Aricept, among other names.

How genes come into it

Donepezil is broken down by the liver enzymes CYP2D6 and CYP3A4. People with low CYP2D6 activity have somewhat higher levels and those with extra copies lower ones, which the US FDA lists as an effect on drug levels; there is no CPIC or DPWG guideline. Studies have also looked at CHAT, the gene for the enzyme that makes acetylcholine, and at BCHE, a second enzyme that breaks it down, for how well donepezil works, with weaker evidence.

Published guidelines

Clinical guidelines that name a gene for Donepezil. They sort people into groups by the gene copies they carry.

US FDA: CYP2D6. CYP2D6 activity score 0 to 6 or more. Data that Demonstrate a Potential Impact on Pharmacokinetic Properties Only.

What research found

Every published finding on gene variants and Donepezil. Upload your DNA file to see which of these rows apply to you.

Rated evidence (5 rated variants)

PharmGKB weighs all studies of a variant and rates how strong the evidence is, from 1A (strongest) to 4.

BCHE rs1803274: Level 3. Efficacy: Alzheimer Disease, Cognitive disorder. 4.

CYP2D6 CYP2D6*1, CYP2D6*1xN, CYP2D6*3, CYP2D6*4, CYP2D6*5, CYP2D6*6: Level 3. Other: Alzheimer Disease. 2.

CHAT rs3793790: Level 3. Efficacy: Alzheimer Disease. 1.

CHRNA7 rs6494223: Level 3. Efficacy: Alzheimer Disease. 1.

Metabolism (21 findings)

Studies of how quickly the body processes this medication.

CYP2D6 CYP2D6 poor metabolizer: CYP2D6 poor metabolizer is associated with decreased metabolism of donepezil in people with Alzheimer Disease as compared to CYP2D6 normal metabolizer.

CYP2D6 CYP2D6*1, CYP2D6*1xN: CYP2D6 *1/*1xN + *1xN/*1xN (assigned as ultrarapid metabolizer phenotype) is associated with increased clearance of donepezil in people with Alzheimer Disease.

CYP2D6 CYP2D6*4, CYP2D6*5: CYP2D6 *4/*4 + *4/*5 (assigned as poor metabolizer phenotype) is associated with decreased clearance of donepezil in people with Alzheimer Disease.

ABCB1 rs1045642: Genotype GG is not associated with clearance of donepezil in people with Alzheimer Disease as compared to genotype AA.

Response (36 findings)

Studies of how well it worked in people carrying a variant.

rs17798800: Allele T is associated with decreased response to donepezil, galantamine and rivastigmine in people with Alzheimer Disease as compared to allele C.

APOE rs429358: Genotypes CC + CT is associated with decreased response to donepezil, galantamine and rivastigmine in people with Alzheimer Disease as compared to genotype TT.

BCHE rs1803274: Allele T is associated with increased response to donepezil in women with Alzheimer Disease as compared to allele C.

CHAT rs2177370: Allele A is associated with increased response to donepezil, galantamine or rivastigmine in people with Alzheimer Disease as compared to allele G.

Study findings and evidence levels: PharmGKB (CC BY-SA 4.0). Guidelines: CPIC and DPWG, as bundled in PharmCAT. Most studies were done mainly in people of European ancestry.

Related Drugs

More drugs from the same category

Exelon (Cholinesterase Inhibitors)

Razadyne (Cholinesterase Inhibitors)

Abilify (Antipsychotics)

Not a prescribing recommendation. This page is educational information about pharmacogenomic research and clinical guidelines - it is not medical or dosing advice, and not a prediction of how any medication will work for you. Never start, stop, or change a medication or dose based on it; talk to your doctor or pharmacist, who can order clinical-grade testing if appropriate.

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Content updated September 2026.

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