DONEPEZIL OXALATE

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 Search

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	( + / - )

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020690s035,021720s008,022568s005lbl.pdf | https://www.ncbi.nlm.nih.gov/pubmed/9428950

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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Acetylcholinesterase 207 Target ID: CHEMBL220 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020690s035,021720s008,022568s005lbl.pdf \| https://www.ncbi.nlm.nih.gov/pubmed/11256231 \| https://www.ncbi.nlm.nih.gov/pubmed/16570913	Inhibitor 8297		6.7 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Alzheimer’s disease 272 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/020690s035,021720s008,022568s005lbl.pdf	Palliative		Approved 8429	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

C_max

Value	Dose	Co-administered	Analyte	Population
34.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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

Value	Dose	Co-administered	Analyte	Population
2889.3 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
72.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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

F_unbound

Value	Dose	Co-administered	Analyte	Population
4.4% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/9839760	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

Dose	Population	Adverse events
175 mg single, transdermal Dose: 175 mg Route: transdermal Route: single Dose: 175 mg Sources: https://pubmed.ncbi.nlm.nih.gov/32440098	healthy, 24.9±3.3 years n = 9 Health Status: healthy Age Group: 24.9±3.3 years Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/32440098	Sources: https://pubmed.ncbi.nlm.nih.gov/32440098
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: https://pubmed.ncbi.nlm.nih.gov/32440098	healthy, 24.9±3.3 years n = 9 Health Status: healthy Age Group: 24.9±3.3 years Sex: M Population Size: 9 Sources: https://pubmed.ncbi.nlm.nih.gov/32440098	Sources: https://pubmed.ncbi.nlm.nih.gov/32440098
23 mg 1 times / day steady, oral Dose: 23 mg, 1 times / day Route: oral Route: steady Dose: 23 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022568Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022568Orig1s000MedR.pdf 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: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2010/022568Orig1s000MedR.pdf Page: p. 50
50 mg single, oral Overdose Dose: 50 mg Route: oral Route: single Dose: 50 mg Sources: https://pubmed.ncbi.nlm.nih.gov/10466911	unhealthy, 79 years n = 1 Health Status: unhealthy Condition: Alzheimer disease Age Group: 79 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/10466911	Other AEs: Nausea, Vomiting... Other AEs: Nausea (1 patient) Vomiting (1 patient) Bradycardia (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/10466911
30 mg 1 times / day steady, oral Dose: 30 mg, 1 times / day Route: oral Route: steady Dose: 30 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/25202036	unhealthy, 80 years n = 1 Health Status: unhealthy Condition: Alzheimer disease Age Group: 80 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/25202036	Disc. AE: Myoclonus... AEs leading to discontinuation/dose reduction: Myoclonus (1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/25202036
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf	unhealthy, adult n = 315 Health Status: unhealthy Age Group: adult Population Size: 315 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf	Other AEs: Diarrhea, Nausea... Other AEs: Diarrhea (3%) Nausea (3%) Vomiting (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf	unhealthy, adult n = 350 Health Status: unhealthy Age Group: adult Population Size: 350 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (<1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2004/21719lbl.pdf

AEs

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:53289	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:53289
ChemicalBook	CB0156314	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0156314
ChemicalBook	CB23334700	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB23334700
ChemicalBook	CB62741796	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB62741796
ChemicalBook	CB73050236	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB73050236
MolPort	MolPort-003-847-014	https://www.molport.com/shop/molecule-link/MolPort-003-847-014
eMolecules	873089	https://www.emolecules.com/cgi-bin/more?vid=873089

PubMed

Title	Date	PubMed
Donepezil hydrochloride: a treatment drug for Alzheimer's disease.	2001	11893059
Selective inhibitors of butyrylcholinesterase: a valid alternative for therapy of Alzheimer's disease?	2001	11888344
Pharmacokinetic profiles of current therapies for Alzheimer's disease: implications for switching to galantamine.	2001	11396867
Clinical and cost-effectiveness of donepezil, rivastigmine and galantamine for Alzheimer's disease: a rapid and systematic review.	2001	11262420
Maintaining functional and behavioral abilities in Alzheimer disease.	2001 Aug	11669508
Maintaining cognitive function in Alzheimer disease: how effective are current treatments?	2001 Aug	11669506
A randomized, double-blind, placebo-controlled study of the efficacy and safety of donepezil in patients with Alzheimer's disease in the nursing home setting.	2001 Dec	11843990
Galantamine: new preparation. The fourth cholinesterase inhibitor for Alzheimer's disease.	2001 Dec	11824442
Donepezil in schizophrenia--is it helpful? An experimental design case study.	2001 Dec	11782241
Successful use of donepezil for the treatment of dementia with Lewy bodies.	2001 Feb	11215841
Effect of donepezil on brain acetylcholinesterase activity in patients with AD measured by PET.	2001 Feb 13	11171913
Chronic donepezil treatment is associated with slowed cognitive decline in Alzheimer's disease.	2001 Jul-Aug	11351141
Central and peripheral activity of cholinesterase inhibitors as revealed by yawning and fasciculation in rats.	2001 Mar	11274994
Amyloid precursor protein in platelets of patients with Alzheimer disease: effect of acetylcholinesterase inhibitor treatment.	2001 Mar	11255448
Open-label, multicenter, phase 3 extension study of the safety and efficacy of donepezil in patients with Alzheimer disease.	2001 Mar	11255446
Structure-based 3D QSAR and design of novel acetylcholinesterase inhibitors.	2001 May	11394735
Donepezil in the treatment of opioid-induced sedation: report of six cases.	2001 May	11369163
Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.	2001 Nov 8	11689088
[Anticholinesterase agents in Alzheimer's disease].	2001 Sep	11680206
Bayesian value-of-information analysis. An application to a policy model of Alzheimer's disease.	2001 Winter	11329844
Economic evaluation of donepezil treatment for Alzheimer's disease in Japan.	2002	11731713
A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.	2002 Mar 12	11889261

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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

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