U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C24H29NO3.C2H2O4
Molecular Weight 469.5268
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DONEPEZIL OXALATE

SMILES

OC(=O)C(O)=O.COC1=CC2=C(C=C1OC)C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)C2

InChI

InChIKey=ZXVUKAUIAFEUEX-UHFFFAOYSA-N
InChI=1S/C24H29NO3.C2H2O4/c1-27-22-14-19-13-20(24(26)21(19)15-23(22)28-2)12-17-8-10-25(11-9-17)16-18-6-4-3-5-7-18;3-1(4)2(5)6/h3-7,14-15,17,20H,8-13,16H2,1-2H3;(H,3,4)(H,5,6)

HIDE SMILES / InChI

Molecular Formula C2H2O4
Molecular Weight 90.0349
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Molecular Formula C24H29NO3
Molecular Weight 379.492
Charge 0
Count
Stereochemistry RACEMIC
Additional Stereochemistry No
Defined Stereocenters 0 / 1
E/Z Centers 0
Optical Activity ( + / - )

Donepezil, marketed under the trade name Aricept, is a medication used in the palliative treatment of Alzheimer's disease. Aricept is indicated for the treatment of dementia of the Alzheimer’s type. Efficacy has been demonstrated in patients with mild to moderate Alzheimer’s Disease, as well as in patients with severe Alzheimer’s Disease. 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. 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.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
ARICEPT

Approved Use

Donepezil hydrochloride orally disintegrating tablets, USP are an acetylcholinesterase inhibitor indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's Disease (1). Donepezil hydrochloride orally disintegrating tablets, USP are indicated for the treatment of dementia of the Alzheimer's type. Efficacy has been demonstrated in patients with mild, moderate, and severe Alzheimer's disease.

Launch Date

1996
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
34.1 ng/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
60.5 ng/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
2889.3 ng × h/mL
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5051.9 ng × h/mL
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
72.7 h
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
73.5 h
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
4.4%
5 mg 1 times / day steady-state, oral
dose: 5 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
4.4%
10 mg 1 times / day steady-state, oral
dose: 10 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DONEPEZIL blood
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
175 mg single, transdermal
Dose: 175 mg
Route: transdermal
Route: single
Dose: 175 mg
Sources:
healthy, 24.9±3.3 years
n = 9
Health Status: healthy
Age Group: 24.9±3.3 years
Sex: M
Population Size: 9
Sources:
175 mg 1 times / 3 days steady, transdermal
Dose: 175 mg, 1 times / 3 days
Route: transdermal
Route: steady
Dose: 175 mg, 1 times / 3 days
Sources:
healthy, 24.9±3.3 years
n = 9
Health Status: healthy
Age Group: 24.9±3.3 years
Sex: M
Population Size: 9
Sources:
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Disc. AE: Bradycardia, Diarrhea...
AEs leading to
discontinuation/dose reduction:
Bradycardia (0.7%)
Diarrhea (1.7%)
Nausea (1.9%)
Vomiting (2.9%)
QT interval prolonged (0.4%)
Anorexia (0.3%)
Dizziness (1.1%)
Headache (0.4%)
Somnolence (0.6%)
Syncope (0.2%)
Aggression (0.5%)
Agitation (0.8%)
Confusional state (0.7%)
Sources: Page: p. 50
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 79 years
Sex: F
Population Size: 1
Sources:
Other AEs: Nausea, Vomiting...
Other AEs:
Nausea (1 patient)
Vomiting (1 patient)
Bradycardia (1 patient)
Sources:
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 80 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 80 years
Sex: F
Population Size: 1
Sources:
Disc. AE: Myoclonus...
AEs leading to
discontinuation/dose reduction:
Myoclonus (1 patient)
Sources:
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
n = 315
Health Status: unhealthy
Age Group: adult
Population Size: 315
Sources:
Other AEs: Diarrhea, Nausea...
Other AEs:
Diarrhea (3%)
Nausea (3%)
Vomiting (2%)
Sources:
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
n = 350
Health Status: unhealthy
Age Group: adult
Population Size: 350
Sources:
Disc. AE: Diarrhea...
AEs leading to
discontinuation/dose reduction:
Diarrhea (<1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Syncope 0.2%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Anorexia 0.3%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Headache 0.4%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
QT interval prolonged 0.4%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Aggression 0.5%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Somnolence 0.6%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Bradycardia 0.7%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Confusional state 0.7%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Agitation 0.8%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Dizziness 1.1%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Diarrhea 1.7%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Nausea 1.9%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Vomiting 2.9%
Disc. AE
23 mg 1 times / day steady, oral
Dose: 23 mg, 1 times / day
Route: oral
Route: steady
Dose: 23 mg, 1 times / day
Sources: Page: p. 50
unhealthy, 73.9 years
n = 967
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 73.9 years
Sex: M+F
Population Size: 967
Sources: Page: p. 50
Bradycardia 1 patient
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 79 years
Sex: F
Population Size: 1
Sources:
Nausea 1 patient
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 79 years
Sex: F
Population Size: 1
Sources:
Vomiting 1 patient
50 mg single, oral
Overdose
Dose: 50 mg
Route: oral
Route: single
Dose: 50 mg
Sources:
unhealthy, 79 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 79 years
Sex: F
Population Size: 1
Sources:
Myoclonus 1 patient
Disc. AE
30 mg 1 times / day steady, oral
Dose: 30 mg, 1 times / day
Route: oral
Route: steady
Dose: 30 mg, 1 times / day
Sources:
unhealthy, 80 years
n = 1
Health Status: unhealthy
Condition: Alzheimer disease
Age Group: 80 years
Sex: F
Population Size: 1
Sources:
Vomiting 2%
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
n = 315
Health Status: unhealthy
Age Group: adult
Population Size: 315
Sources:
Diarrhea 3%
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
n = 315
Health Status: unhealthy
Age Group: adult
Population Size: 315
Sources:
Nausea 3%
10 mg 1 times / day steady, oral
Recommended
Dose: 10 mg, 1 times / day
Route: oral
Route: steady
Dose: 10 mg, 1 times / day
Sources:
unhealthy, adult
n = 315
Health Status: unhealthy
Age Group: adult
Population Size: 315
Sources:
Diarrhea <1%
Disc. AE
5 mg 1 times / day steady, oral
Recommended
Dose: 5 mg, 1 times / day
Route: oral
Route: steady
Dose: 5 mg, 1 times / day
Sources:
unhealthy, adult
n = 350
Health Status: unhealthy
Age Group: adult
Population Size: 350
Sources:
PubMed

PubMed

TitleDatePubMed
Donepezil hydrochloride: a treatment drug for Alzheimer's disease.
2001
The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia.
2001
Muscarinic agonists and antagonists in the treatment of Alzheimer's disease.
2001 Apr
Maintaining functional and behavioral abilities in Alzheimer disease.
2001 Aug
Maintaining cognitive function in Alzheimer disease: how effective are current treatments?
2001 Aug
Prevalence, costs, and treatment of Alzheimer's disease and related dementia: a managed care perspective.
2001 Aug
Medications for the treatment of Alzheimer's disease.
2001 Aug
Motor cortex disinhibition in Alzheimer's disease.
2001 Aug
A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.
2001 Aug 14
A 1-year, placebo-controlled preservation of function survival study of donepezil in AD patients.
2001 Aug 14
Randomized placebo-controlled trial of donepezil in patients with progressive supranuclear palsy.
2001 Aug 14
A 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.
2001 Aug 28
Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's disease.
2001 Dec
Unsafe prescription medication switching recommendations.
2001 Dec
Donepezil in schizophrenia--is it helpful? An experimental design case study.
2001 Dec
Alzheimer's disease: recent advances in etiology, diagnosis, and management.
2001 Dec
[Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors and gingko].
2001 Dec 13
[A patient with probable dementia with Lewy bodies, who showed improvement of dementia and parkinsonism by the administratim of donepezil].
2001 Jul
Pisa syndrome due to a cholinesterase inhibitor (donepezil): a case report.
2001 Jul
[Aphasia and dementia].
2001 Jul
Open-label study of donepezil in traumatic brain injury.
2001 Jul
Equity in the new NHS: hard lessons from implementing a local healthcare policy on donepezil.
2001 Jul 28
Newest developments in dementia treatment and prevention.
2001 Jul-Aug
An open-label, 24-week pilot study of the methyl donor betaine in Alzheimer disease patients.
2001 Jul-Sep
Cholinergic modulation of speed of early information processing: the effect of donepezil on inspection time.
2001 Jun
Actigraphic sleep-wake patterns and urinary 6-sulfatoxymelatonin excretion in patients with Alzheimer's disease.
2001 May
Equity in the new NHS. Evidence cannot help in all situations.
2001 Nov 10
[A comparison of cholinesterase inhibitors and ginkgo extract in treatment of Alzheimer dementia].
2001 Nov 29
A case of Korsakoff's syndrome improved by high doses of donepezil.
2001 Nov-Dec
Treatment of tardive dyskinesia with donepezil: a pilot study.
2001 Oct
[Effectiveness of donepezil on several cognitive functions in patients with Alzheimer's disease over 12 months].
2001 Oct
Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.
2001 Oct
[Relief for caregivers. Anti-dementia drug saves costs].
2001 Oct 18
Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles.
2001 Winter
Economic evaluation of donepezil treatment for Alzheimer's disease in Japan.
2002
Donepezil management of schizophrenia with associated dementia.
2002 Apr
Donepezil in the treatment of Alzheimer's disease: long-term efficacy and safety.
2002 Feb
Feasibility of vascular dementia treatment with cholinesterase inhibitors.
2002 Feb
Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease.
2002 Feb 8
[Pharmacotherapy for the treatment of Alzheimer's disease--the present state and the development in the future].
2002 Jan
A new HPLC method to determine Donepezil hydrochloride in tablets.
2002 Jan 1
Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease.
2002 Jan-Feb
Lewy body dementia: case report and discussion.
2002 Jan-Feb
How many patients complete an adequate trial of donepezil?
2002 Jan-Mar
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study.
2002 Mar
Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients.
2002 Mar
A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia.
2002 Mar 1
A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.
2002 Mar 12
In vitro toxicity of rivastigmine and donepezil in cells of epithelial origin.
2002 Mar-Apr
Donepezil improved the clinical state and quality of life in moderate-to-severe Alzheimer disease.
2002 Mar-Apr
Patents

Sample Use Guides

Mild to Moderate Alzheimer’s Disease - 5 mg or 10 mg administered once daily Moderate to Severe Alzheim er’s Disease - 10 mg or 23 mg administered once daily A dose of 10 mg once daily can be administered once patients have been on a daily dose of 5 mg for 4 to 6 weeks. A dose of 23 mg once daily can be administered once patien ts have been on a dose of 10 mg once daily for at least 3 months
Route of Administration: Oral
Donepezil inhibited freshly prepared human erythrocyte AChE with IC50 22 nM
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:45:46 GMT 2023
Edited
by admin
on Fri Dec 15 16:45:46 GMT 2023
Record UNII
SLF7M28SI5
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DONEPEZIL OXALATE
WHO-DD  
Common Name English
DONEPEZIL MONOXALATE
Common Name English
Donepezil oxalate [WHO-DD]
Common Name English
1H-INDEN-1-ONE, 2,3-DIHYDRO-5,6-DIMETHOXYL-2-((1-(PHENYLMETHYL)-4-PIPERIDINYL)METHYL)-, ETHANEDOIOATE (1:1)
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C47792
Created by admin on Fri Dec 15 16:45:47 GMT 2023 , Edited by admin on Fri Dec 15 16:45:47 GMT 2023
Code System Code Type Description
NCI_THESAURUS
C87489
Created by admin on Fri Dec 15 16:45:47 GMT 2023 , Edited by admin on Fri Dec 15 16:45:47 GMT 2023
PRIMARY
CAS
870555-76-3
Created by admin on Fri Dec 15 16:45:47 GMT 2023 , Edited by admin on Fri Dec 15 16:45:47 GMT 2023
PRIMARY
PUBCHEM
11397232
Created by admin on Fri Dec 15 16:45:47 GMT 2023 , Edited by admin on Fri Dec 15 16:45:47 GMT 2023
PRIMARY
FDA UNII
SLF7M28SI5
Created by admin on Fri Dec 15 16:45:47 GMT 2023 , Edited by admin on Fri Dec 15 16:45:47 GMT 2023
PRIMARY
Related Record Type Details
PARENT -> SALT/SOLVATE
Related Record Type Details
ACTIVE MOIETY