PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
donepezil

2D structure

Overview

Trade Names: Aricept; Aricept ODT; Eranz
PharmGKB Accession Id: PA449394

Description

Donepezil (Aricept), is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. Donepezil has been tested in other cognitive disorders including Lewy body dementia and Vascular dementia, but it is not currently approved for these indications. Donepezil has also been studied in patients with Mild Cognitive Impairment, schizophrenia, attention deficit disorder, post-coronary bypass cognitive impairment, cognitive impairment associated with multiple sclerosis, and Down syndrome. (source: Drug Bank)

Indication

For management of symptoms associated with Alzheimer's Disease (source: Drug Bank)

ATC Therapeutic Category

  • N06DA:Anticholinesterases

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Donepezil's proposed mechanism of action involves the increase of the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. (source: Drug Bank)

Pharmacology

Donepezil is a centrally acting reversible acetyl cholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. It is well absorbed in the gut with an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks. Donepezil is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. Donepezil is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, donepezil's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that donepezil alters the course of the underlying dementing process. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Take without regard to meals. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Donepezil is metabolized by CYP 450 isoenzymes 2D6 and 3A4 in the liver and also undergoes glucuronidation. The main metabolite, 6-O-desmethyl donepezil, has been reported to inhibit AChE to the same extent as donepezil in vitro. (source: Drug Bank)

Protein Binding

96% (source: Drug Bank)

Absorption

Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours. (source: Drug Bank)

Toxicity

Symptoms of overdose include severe nausea, vomiting, salivation, sweating, bradycardia, hypotension, respiratory depression, collapse and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. (source: Drug Bank)

Isomeric SMILES Code:

COc1cc2c(cc1OC)C(=O)C(C2)CC3CCN(CC3)Cc4ccccc4 (source: Drug Bank)

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
APOE
  • CO
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
BCHE
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CHAT
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data Genotype Data Available Literature annotations available Not annotated
CYP1A2
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  •   
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  •   
  • PD
  • PK
  • FA
  •   
Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
HTR2A Uncurated Annotation (source: Drug Bank)
ACHE Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
carbamazepine
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  • PK
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
ketoconazole
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  • PK
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No phenotype data No genotype data Literature annotations available Not annotated
oxcarbazepine
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  • PK
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenobarbital
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  • PK
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
phenytoin
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  • PK
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
quinidine
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  • PK
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Phenotype data available Genotype Data Available Literature annotations available Not annotated
rifampin
  •   
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  • PK
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No phenotype data No genotype data Literature annotations available Not annotated
st. john's wort
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  • PK
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No phenotype data No genotype data Literature annotations available Not annotated
tacrine
  •   
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  • PK
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Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
amantadine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
amitriptyline Uncurated Annotation Possible antagonism of action (source: Drug Bank)
amoxapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
atropine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
benztropine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
biperiden Uncurated Annotation Possible antagonism of action (source: Drug Bank)
brompheniramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
chlorpheniramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
chlorpromazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
cimetidine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
clomipramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
clozapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
cyclobenzaprine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
desipramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
dimenhydrinate Uncurated Annotation Possible antagonism of action (source: Drug Bank)
diphenhydramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
disopyramide Uncurated Annotation Possible antagonism of action (source: Drug Bank)
doxepin Uncurated Annotation Possible antagonism of action (source: Drug Bank)
doxylamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
ethopropazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
flupenthixol Uncurated Annotation Possible antagonism of action (source: Drug Bank)
hydroxyzine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
imipramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
isocarboxazid Uncurated Annotation Possible antagonism of action (source: Drug Bank)
loxapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
maprotiline Uncurated Annotation Possible antagonism of action (source: Drug Bank)
meclizine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
meperidine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
mesoridazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
mirtazapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
moclobemide Uncurated Annotation Possible antagonism of action (source: Drug Bank)
nortriptyline Uncurated Annotation Possible antagonism of action (source: Drug Bank)
olanzapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
orphenadrine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
perphenazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
phenelzine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
pimozide Uncurated Annotation Possible antagonism of action (source: Drug Bank)
pipotiazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
procainamide Uncurated Annotation Possible antagonism of action (source: Drug Bank)
prochlorperazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
promazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
promethazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
protriptyline Uncurated Annotation Possible antagonism of action (source: Drug Bank)
quetiapine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
quinidine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
risperidone Uncurated Annotation Possible antagonism of action (source: Drug Bank)
scopolamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
scopolamine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
sertraline Uncurated Annotation Possible antagonism of action (source: Drug Bank)
thioridazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
thiothixene Uncurated Annotation Possible antagonism of action (source: Drug Bank)
tizanidine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
tranylcypromine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
trazodone Uncurated Annotation Possible antagonism of action (source: Drug Bank)
trifluoperazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
triflupromazine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
trimipramine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
triprolidine Uncurated Annotation Possible antagonism of action (source: Drug Bank)
ziprasidone Uncurated Annotation Possible antagonism of action (source: Drug Bank)
zuclopenthixol Uncurated Annotation Possible antagonism of action (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Alzheimer Disease
  • CO
  • PD
  •   
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Dementia
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Neurodegenerative Diseases
  • CO
  •   
  •   
  •   
  •   
Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB00843
KEGG Drug ID:
D00670
PubChem Compound ID:
3152
PubChem Substance ID:
207105

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

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