DONEPEZIL HYDROCHLORIDE MONOHYDRATE

Details

Stereochemistry	RACEMIC
Molecular Formula	C24H29NO3.ClH.H2O
Molecular Weight	433.968
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of DONEPEZIL HYDROCHLORIDE MONOHYDRATE

Structure Search

SMILES

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

InChI

InChIKey=HLJIZAKUNCTCQX-UHFFFAOYSA-N

InChI=1S/C24H29NO3.ClH.H2O/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;;/h3-7,14-15,17,20H,8-13,16H2,1-2H3;1H;1H2

HIDE SMILES / InChI

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
The beneficial effect of cholinesterase inhibitors on patients suffering from Parkinson's disease and dementia.	2001	11768630
EEG changes during long-term treatment with donepezil in Alzheimer's disease patients.	2001	11725819
Galantamine for Alzheimer's disease.	2001	11687119
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 24-week, randomized, double-blind study of donepezil in moderate to severe Alzheimer's disease.	2001 Aug 28	11524468
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
Unsafe prescription medication switching recommendations.	2001 Dec	11813938
Donepezil in schizophrenia--is it helpful? An experimental design case study.	2001 Dec	11782241
Alzheimer's disease: recent advances in etiology, diagnosis, and management.	2001 Dec	11767466
[Alzheimer dementia. Comparison of the effectiveness of cholinesterase inhibitors and gingko].	2001 Dec 13	11824165
[A patient with probable dementia with Lewy bodies, who showed improvement of dementia and parkinsonism by the administratim of donepezil].	2001 Jul	11808350
Featured CME topic: dementia. Medication update.	2001 Jul	11531174
Ameliorative effects of azaindolizinone derivative ZSET845 on scopolamine-induced deficits in passive avoidance and radial-arm maze learning in the rat.	2001 Nov	11885975
[Malignant syndrome caused by a combination of bromperidol and donepezil hydrochloride in a patient with probable dementia with Lewy bodies].	2001 Nov	11774731
Cerebrospinal fluid acetylcholinesterase activity after long-term treatment with donepezil and rivastigmina.	2001 Nov	11589922
Platelet amyloid precursor protein forms in AD: a peripheral diagnostic tool and a pharmacological target.	2001 Nov	11589917
Equity in the new NHS. Evidence cannot help in all situations.	2001 Nov 10	11725754
SCH 57790, a selective muscarinic M(2) receptor antagonist, releases acetylcholine and produces cognitive enhancement in laboratory animals.	2001 Nov 16	11728425
[A comparison of cholinesterase inhibitors and ginkgo extract in treatment of Alzheimer dementia].	2001 Nov 29	11789125
Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil.	2001 Nov 8	11689088
[Risperidone in the ambulatory treatment of behavior disorders in demented patients of Alzheimer's type: a retrospective analysis].	2001 Nov-Dec	11877883
A case of Korsakoff's syndrome improved by high doses of donepezil.	2001 Nov-Dec	11704621
Treatment of tardive dyskinesia with donepezil: a pilot study.	2001 Oct	11816865
[Effectiveness of donepezil on several cognitive functions in patients with Alzheimer's disease over 12 months].	2001 Oct	11738011
Donepezil hydrochloride preserves regional cerebral blood flow in patients with Alzheimer's disease.	2001 Oct	11585854
[Relief for caregivers. Anti-dementia drug saves costs].	2001 Oct 18	11697297
[Anticholinesterase agents in Alzheimer's disease].	2001 Sep	11680206
Donepezil for Alzheimer's disease: pharmacodynamic, pharmacokinetic, and clinical profiles.	2001 Winter	11830754
Economic evaluation of donepezil treatment for Alzheimer's disease in Japan.	2002	11731713
Donepezil management of schizophrenia with associated dementia.	2002 Apr	11910273
Donepezil in the treatment of Alzheimer's disease: long-term efficacy and safety.	2002 Feb	11817515
Feasibility of vascular dementia treatment with cholinesterase inhibitors.	2002 Feb	11813286
Atrophy of the substantia innominata on magnetic resonance imaging and response to donepezil treatment in Alzheimer's disease.	2002 Feb 8	11814647
[Pharmacotherapy for the treatment of Alzheimer's disease--the present state and the development in the future].	2002 Jan	11808319
A new HPLC method to determine Donepezil hydrochloride in tablets.	2002 Jan 1	11682224
[Alzheimer dementia. Intervening as early as possible].	2002 Jan 17	11847891
Therapeutic effects of an acetylcholinesterase inhibitor (donepezil) on memory in Wernicke-Korsakoff's disease.	2002 Jan-Feb	11852291
Lewy body dementia: case report and discussion.	2002 Jan-Feb	11841138
How many patients complete an adequate trial of donepezil?	2002 Jan-Mar	11882749
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Down syndrome and Alzheimer's disease--pilot study.	2002 Mar	11921156
Comparison of citalopram, perphenazine, and placebo for the acute treatment of psychosis and behavioral disturbances in hospitalized, demented patients.	2002 Mar	11870012
A double blind placebo controlled trial of donepezil adjunctive treatment to risperidone for the cognitive impairment of schizophrenia.	2002 Mar 1	11904128
A 1-year, randomized, placebo-controlled study of donepezil in patients with mild to moderate AD.	2002 Mar 12	11889261
Determination of donepezil, an acetylcholinesterase inhibitor, in human plasma by high-performance liquid chromatography with ultraviolet absorbance detection.	2002 Mar 5	11888054
In vitro toxicity of rivastigmine and donepezil in cells of epithelial origin.	2002 Mar-Apr	11914613
Donepezil improved the clinical state and quality of life in moderate-to-severe Alzheimer disease.	2002 Mar-Apr	11874284

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

Name

Type

Language

DONEPEZIL HYDROCHLORIDE MONOHYDRATE

Common Name

English

DONEPEZIL HYDROCHLORIDE MONOHYDRATE [EP MONOGRAPH]

Common Name

English

1H-INDEN-1-ONE, 2,3-DIHYDRO-5,6-DIMETHOXY-2-((1-(PHENYLMETHYL)-4-PIPERIDINYL)METHYL)-, HYDROCHLORIDE, HYDRATE (1:1:1)

Systematic Name

English

Donepezil hydrochloride monohydrate [WHO-DD]

Common Name

English

1H-INDEN-1-ONE, 2,3-DIHYDRO-5,6-DIMETHOXY-2-((1-(PHENYLMETHYL)-4-PIPERIDINYL)METHYL)-, HYDROCHLORIDE, MONOHYDRATE

Systematic Name

English

Code System Code Type Description

FDA UNII

7KZL5YRL6W