Identification

Name
Donepezil
Accession Number
DB00843  (APRD00039)
Type
Small Molecule
Groups
Approved
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.

Structure
Thumb
Synonyms
  • Domepezil
  • Donepezil
  • Donepezilo
  • Donepezilum
External IDs
BNAG / E 2020
Product Ingredients
IngredientUNIICASInChI Key
Donepezil hydrochloride3O2T2PJ89D120011-70-3XWAIAVWHZJNZQQ-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act DonepezilTablet10 mgOralActavis Pharma Company2013-12-27Not applicableCanada
Act DonepezilTablet5 mgOralActavis Pharma Company2013-12-27Not applicableCanada
Act Donepezil ODTTablet, orally disintegrating10 mgOralTeva2013-12-27Not applicableCanada
Act Donepezil ODTTablet, orally disintegrating5 mgOralTeva2013-12-27Not applicableCanada
AriceptTablet5 mgOralPfizer1997-08-20Not applicableCanada
AriceptTablet, film coated23 mg/1OralEisai Limited2010-07-23Not applicableUs62856 0247 90 nlmimage10 c412e257
AriceptTablet, film coated10 mg/1Oralbryant ranch prepack1996-11-252018-09-10Us
AriceptTablet, film coated23 mg/1OralAvera McKennan Hospital2015-03-232018-06-26Us
AriceptTablet, film coated5 mg/1OralCardinal Health1996-11-262014-11-30Us
AriceptTablet, film coated10 mg/1OralEisai Limited1996-11-25Not applicableUs
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-donepezilTablet10 mgOralAccel Pharma Inc2014-09-04Not applicableCanada
Accel-donepezilTablet5 mgOralAccel Pharma Inc2014-09-04Not applicableCanada
Ag-donepezilTablet5 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-donepezilTablet10 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Apo-donepezilTablet5 mgOralApotex Corporation2013-12-27Not applicableCanada
Apo-donepezilTablet10 mgOralApotex Corporation2014-12-27Not applicableCanada
Auro-donepezilTablet5 mgOralAuro Pharma Inc2013-12-27Not applicableCanada
Auro-donepezilTablet10 mgOralAuro Pharma Inc2013-12-27Not applicableCanada
Bio-donepezilTablet10 mgOralBiomed Pharma2013-12-27Not applicableCanada
Bio-donepezilTablet5 mgOralBiomed Pharma2013-12-27Not applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals2017-02-01Not applicableUs
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (28 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals2017-02-01Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (21 mg/1)CapsuleOralAllergan2016-07-18Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1)CapsuleOralAllergan2014-12-24Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1) + Memantine Hydrochloride (28 mg/1) + Memantine Hydrochloride (7 mg/1) + Memantine Hydrochloride (21 mg/1)KitOralAllergan2016-11-28Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (7 mg/1)CapsuleOralAllergan2016-07-18Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1) + Memantine Hydrochloride (28 mg/1) + Memantine Hydrochloride (7 mg/1) + Memantine Hydrochloride (21 mg/1)KitOralAllergan2016-11-28Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1) + Memantine Hydrochloride (28 mg/1) + Memantine Hydrochloride (7 mg/1) + Memantine Hydrochloride (21 mg/1)KitOralAllergan2016-11-28Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (28 mg/1)CapsuleOralAllergan2014-12-24Not applicableUs
NamzaricDonepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Donepezil hydrochloride (10 mg/1) + Memantine Hydrochloride (14 mg/1) + Memantine Hydrochloride (28 mg/1) + Memantine Hydrochloride (7 mg/1) + Memantine Hydrochloride (21 mg/1)KitOralAllergan2016-11-28Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Donepezil HydrochlorideDonepezil hydrochloride (5 mg/1)Tablet, film coatedOralTeva2011-04-142011-04-14Us
Donepezil HydrochlorideDonepezil hydrochloride (10 mg/1)Tablet, film coatedOralTeva2011-04-142011-04-14Us
International/Other Brands
Alzepil (Egis) / Davia (Terapia) / Depzil (Psyco Remedies) / Donecept (Actavis) / Donecil (ABL Pharma) / Donep (Alkem) / Donepex (Schafer) / Donesyn (Synthon) / Dopezil (Medis) / Eranz (Wyeth) / Memac (Pfizer) / Nomi-Nox (Johnson) / Pezale (Sandoz) / Redumas (Teva) / Zolpezil (Actavis)
Categories
UNII
8SSC91326P
CAS number
120014-06-4
Weight
Average: 379.492
Monoisotopic: 379.214743799
Chemical Formula
C24H29NO3
InChI Key
ADEBPBSSDYVVLD-UHFFFAOYSA-N
InChI
InChI=1S/C24H29NO3/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
IUPAC Name
2-[(1-benzylpiperidin-4-yl)methyl]-5,6-dimethoxy-2,3-dihydro-1H-inden-1-one
SMILES
COC1=C(OC)C=C2C(=O)C(CC3CCN(CC4=CC=CC=C4)CC3)CC2=C1

Pharmacology

Indication

For the palliative treatment of mild to moderate dementia of the Alzheimer's type.

Associated Conditions
Pharmacodynamics

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. An early pathophysiological feature of Alzheimer's disease that is associated with memory loss and cognitive deficits is a deficiency of acetylcholine as a result of selective loss of cholinergic neurons in the cerebral cortex, nucleus basalis, and hippocampus. 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 progresses and fewer cholinergic neurons remain functionally intact. There is no evidence that donepezil alters the course of the underlying dementing process.

Mechanism of action

Donepezil is a piperidine derivative that is a centerally active, reversible inhibitor of acetylcholinesterase. This drug is structurally unrelated to other anticholinesterase agents. Donepezil's proposed mechanism of action involves the reversible inhibition of cholinesterases (eg. acetylcholinesterase), which prevents the hydrolysis of acetycholine, and leads to an increased concentration of acetylcholine at cholinergic synapses. Evidence suggests that the anticholinesterase activity of donepezil is relatively specific for acetylcholinesterase in the brain.

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Human
U5-hydroxytryptamine receptor 2A
other/unknown
Human
Absorption

Donepezil is well absorbed with a relative oral bioavailability of 100% and reaches peak plasma concentrations in 3 to 4 hours.

Volume of distribution
  • 12 L/kg
Protein binding

96%

Metabolism

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.

Route of elimination

Donepezil is both excreted in the urine intact and extensively metabolized to four major metabolites, two of which are known to be active, and a number of minor metabolites, not all of which have been identified.

Half life

70 hours

Clearance
  • apparent plasma cl=0.13 L/hr/kg
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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*2A(C;G) / (G;G)C > GEffect Directly StudiedPatients with this genotype are have a decreased likelihood of responding to donepezil when treating Alzheimer's disease.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Donepezil.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Donepezil.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Donepezil is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Donepezil is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Donepezil.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Donepezil is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Donepezil.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Donepezil is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Donepezil.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Donepezil is combined with 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
  • Avoid alcohol.
  • Take without regard to meals.

References

Synthesis Reference

Akio Imai, Hideaki Watanabe, Takashi Kajima, Yasushi Ishihama, Akiyo Ohtsuka, Tomohide Tanaka, Yukio Narabu, "Polymorphs of donepezil hydrochloride and process for production." U.S. Patent US5985864, issued December, 1988.

US5985864
General References
  1. Xiong G, Doraiswamy PM: Combination drug therapy for Alzheimer's disease: what is evidence-based, and what is not? Geriatrics. 2005 Jun;60(6):22-6. [PubMed:15948662]
  2. Yesavage JA, Mumenthaler MS, Taylor JL, Friedman L, O'Hara R, Sheikh J, Tinklenberg J, Whitehouse PJ: Donepezil and flight simulator performance: effects on retention of complex skills. Neurology. 2002 Jul 9;59(1):123-5. [PubMed:12105320]
  3. Sugimoto H: Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Chem Rec. 2001;1(1):63-73. [PubMed:11893059]
External Links
Human Metabolome Database
HMDB0005041
KEGG Drug
D00670
PubChem Compound
3152
PubChem Substance
46504803
ChemSpider
3040
BindingDB
8960
ChEBI
53289
ChEMBL
CHEMBL502
Therapeutic Targets Database
DAP000560
PharmGKB
PA449394
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Donepezil
ATC Codes
N06DA02 — DonepezilN06DA53 — Donepezil, memantine and ginkgo foliumN06DA52 — Donepezil and memantine
AHFS Codes
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
FDA label
Download (303 KB)
MSDS
Download (58.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceAlzheimer's Disease (AD)1
0CompletedSupportive CareBrain and Central Nervous System Tumors / Cognitive/Functional Effects / Long-Term Effects Secondary to Cancer Therapy in Children / Neurologic toxicity / Psychosocial Effects of Cancer and Its Treatment / Radiation Toxicity1
0RecruitingBasic ScienceParkinson's Disease (PD)1
0Unknown StatusBasic ScienceHealthy Volunteers1
1Active Not RecruitingTreatmentDementia, Vascular / Memory Disturbances / Strokes1
1CompletedNot AvailableAdults / Healthy Volunteers1
1CompletedNot AvailableAlzheimer's Disease (AD)2
1CompletedNot AvailableCognitive Impairments1
1CompletedNot AvailableHealthy Adults2
1CompletedNot AvailableHealthy Volunteers8
1CompletedBasic ScienceCognition1
1CompletedBasic ScienceHealthy Volunteers1
1CompletedBasic SciencePain, Neuropathic1
1CompletedDiagnosticDementias1
1CompletedHealth Services ResearchAlzheimer's Disease (AD)1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentAlzheimer's Disease (AD)7
1CompletedTreatmentAlzheimer's Disease (AD) / Battery1
1CompletedTreatmentAlzheimer's Disease (AD) / Central Nervous System Diseases1
1CompletedTreatmentAlzheimer's Disease (AD) / Memory Disturbances1
1CompletedTreatmentDementias1
1CompletedTreatmentFragile X Syndrome (FXS)1
1CompletedTreatmentHealthy Elderly Male1
1CompletedTreatmentHealthy Volunteers6
1Not Yet RecruitingTreatmentAlzheimer's Disease (AD) / Mild Cognitive Impairment (MCI)1
1RecruitingNot AvailableAlzheimer's Disease (AD)1
1RecruitingBasic ScienceHealthy Volunteers1
1RecruitingTreatmentAlzheimer's Disease (AD) / Cognitive Impairments1
1RecruitingTreatmentAlzheimer's Disease (AD) / Healthy Volunteers1
1RecruitingTreatmentAmblyopia1
1TerminatedBasic ScienceAlzheimer's Disease (AD)1
1TerminatedTreatmentAlzheimer's Disease (AD) / Dementias1
1WithdrawnTreatmentAlzheimer's Disease (AD)1
1, 2CompletedNot AvailableAutism, Early Infantile / Cognition Disorder1
1, 2Unknown StatusTreatmentStroke, Acute1
2Active Not RecruitingTreatmentMild-Moderate Alzheimer's Disease1
2CompletedDiagnosticAlzheimer's Disease (AD)1
2CompletedPreventionDelirium1
2CompletedSupportive CareBrain and Central Nervous System Tumors / Radiation Toxicity1
2CompletedSupportive CareSmoking1
2CompletedTreatmentAlzheimer's Disease (AD)13
2CompletedTreatmentAnxiety Disorders / Cancer, Breast / Cognition Disorders / Depression / Sleep disorders and disturbances / Tiredness1
2CompletedTreatmentAutistic Disorder1
2CompletedTreatmentCocaine Abuse and Dependence1
2CompletedTreatmentCocaine Use Disorders1
2CompletedTreatmentCognitive Impairments1
2CompletedTreatmentDementia Alzheimer's Type1
2CompletedTreatmentDementia With Lewy Bodies (DLB)2
2CompletedTreatmentDown Syndrome (DS)1
2CompletedTreatmentFragile X Syndrome (FXS)1
2CompletedTreatmentIrritation/Irritant1
2CompletedTreatmentMigrainous Headache1
2CompletedTreatmentPost-traumatic Neuropathic Pain1
2CompletedTreatmentStroke, Ischemic1
2Not Yet RecruitingTreatmentAlzheimer's Disease (AD)1
2RecruitingTreatmentAutism Spectrum Conditions/Disorders1
2RecruitingTreatmentCognitive Impairments1
2RecruitingTreatmentParkinson's Disease (PD)3
2TerminatedBasic ScienceAlzheimer's Disease (AD)1
2TerminatedTreatmentAlzheimer's Disease (AD)3
2TerminatedTreatmentAneurysmal Subarachnoid Hemorrhage / Delayed Cerebral Ischemia / Delayed Neurological Deficit / Vasospasm1
2TerminatedTreatmentAutism Spectrum Conditions/Disorders1
2TerminatedTreatmentDown Syndrome (DS)1
2TerminatedTreatmentSchizophrenic Disorders1
2Unknown StatusTreatmentAlzheimer's Disease (AD) / Memory Disorders1
2Unknown StatusTreatmentSupranuclear Palsy, Progressive1
2WithdrawnTreatmentParkinson's Disease (PD)1
2, 3RecruitingTreatmentAlzheimer's1
3CompletedSupportive CareBrain and Central Nervous System Tumors / Cognitive/Functional Effects / Metastatic Cancers / Metastatic Disease / Neoplasms, Brain / Psychosocial Effects of Cancer and Its Treatment / Radiation Toxicity / Tiredness1
3CompletedSupportive CareCognitive/Functional Effects / Delirium / Depression / Lung Cancers / Radiation Toxicity1
3CompletedTreatmentAlzheimer's Disease (AD)5
3CompletedTreatmentAlzheimer's Disease (AD) / Dementias2
3CompletedTreatmentAttention Impairment1
3CompletedTreatmentDementia Associated With Cerebrovascular Disease1
3CompletedTreatmentDementia With Lewy Bodies (DLB)1
3CompletedTreatmentDementia With Parkinson's Disease1
3CompletedTreatmentDementia, Alzheimer Type1
3CompletedTreatmentDementia, Vascular2
3CompletedTreatmentMild Cognitive Impairment (MCI)1
3Not Yet RecruitingPreventionFemoral Head Necrosis / Osteoarthritis (OA) / Rheumatoid Arthritis1
3RecruitingTreatmentAlzheimer's Disease (AD)2
3RecruitingTreatmentCognitive Dysfunctions / Memory Disturbances1
3RecruitingTreatmentMemory Disturbances / Traumatic Brain Injury (TBI)1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3TerminatedTreatmentCancer, Advanced1
3TerminatedTreatmentCognitive Dysfunctions / Down Syndrome (DS)1
3TerminatedTreatmentCognitive Dysfunctions / Down Syndrome (DS) / Down Syndrome, Cognitive Dysfunction1
3TerminatedTreatmentDementia, Mixed / Dementia, Vascular1
3TerminatedTreatmentParkinson's Disease (PD)1
3Unknown StatusTreatmentDementia of Alzheimer's Type1
3Unknown StatusTreatmentRett's Syndrome1
3Unknown StatusTreatmentStroke, Ischemic1
3WithdrawnTreatmentDisseminated Sclerosis1
4Active Not RecruitingOtherAlzheimer's Disease (AD)1
4Active Not RecruitingPreventionAlzheimer's Disease (AD) / Delirium, Dementia, Amnestic, Cognitive Disorders / Mild Cognitive Impairment (MCI)1
4Active Not RecruitingTreatmentAlzheimer's Disease (AD)1
4Active Not RecruitingTreatmentDementia Associated With Cerebrovascular Disease1
4Active Not RecruitingTreatmentPain, Neuropathic1
4CompletedBasic ScienceSleep Deprivation1
4CompletedPreventionCognition Disorders1
4CompletedPreventionCognitively Normal Elderly Individuals1
4CompletedPreventionDelirium / Postoperative Complications2
4CompletedSupportive CareGeriatrics / Mental Health1
4CompletedTreatmentAlzheimer's Disease (AD)6
4CompletedTreatmentAlzheimer's Disease (AD) / Cognition Disorders1
4CompletedTreatmentAlzheimer's Disease (AD) / Sleep Apnea, Obstructive1
4CompletedTreatmentAphasia / Strokes1
4CompletedTreatmentBipolar Disorder (BD) / Mania1
4CompletedTreatmentCerebrovascular Accidents1
4CompletedTreatmentDementia, Alzheimer Type1
4CompletedTreatmentDementia, Vascular1
4CompletedTreatmentDementias1
4CompletedTreatmentDementias / Depression1
4CompletedTreatmentDepression / Mild Cognitive Impairment (MCI)1
4CompletedTreatmentEnd-Stage Renal Disease (ESRD)1
4CompletedTreatmentMemory1
4CompletedTreatmentMemory Losses1
4CompletedTreatmentMild Cognitive Impairment (MCI)2
4CompletedTreatmentMild to Severe Alzheimer's Disease1
4CompletedTreatmentObstructive Sleep Apnea (OSA)1
4CompletedTreatmentParkinson's Disease (PD)1
4Not Yet RecruitingTreatmentAlzheimer's Disease (AD) / Cognitive Function1
4Not Yet RecruitingTreatmentOSA / Sleepiness1
4RecruitingBasic ScienceAmblyopia1
4RecruitingOtherGenetic Risk for Alzheimer's Disease1
4RecruitingTreatmentParkinson's Disease (PD)1
4TerminatedTreatmentAlzheimer's Disease (AD)2
4TerminatedTreatmentBack Pain Lower Back Chronic / Diabetic Neuropathic Pain1
4TerminatedTreatmentDelirium of Unknown (Axis III) Etiology / Elderly / Intensive Care (ICU) Myopathy1
4Unknown StatusPreventionAlzheimer's Disease (AD)1
4Unknown StatusTreatmentAlzheimer's Disease (AD) / Dementias1
4Unknown StatusTreatmentImpaired Cognition / Schizophrenic Disorders1
4Unknown StatusTreatmentModerate to Severe Alzheimer's Disease1
4Unknown StatusTreatmentObstructive Sleep Apnea (OSA)1
4Unknown StatusTreatmentParkinson's Disease (PD)1
4Unknown StatusTreatmentSchizoaffective Disorders / Schizophrenic Disorders / Schizophreniform Disorder1
4WithdrawnTreatmentAlzheimer's Disease (AD)1
4WithdrawnTreatmentSevere Alzheimer's Disease1
Not AvailableActive Not RecruitingNot AvailableDementia With Lewy Body Disease1
Not AvailableActive Not RecruitingPreventionBalance / Falls / Gait / Mild Cognitive Impairment (MCI)1
Not AvailableCompletedNot AvailableAlzheimer's Desease1
Not AvailableCompletedNot AvailableAlzheimer's Disease (AD)4
Not AvailableCompletedNot AvailableAlzheimer's Disease (AD) / Dementias1
Not AvailableCompletedNot AvailableBiomarkers, Pharmacological1
Not AvailableCompletedNot AvailableCholinergic Function1
Not AvailableCompletedNot AvailableDiffuse Lewy Body Disease1
Not AvailableCompletedPreventionElderly1
Not AvailableCompletedSupportive CareDementia With Lewy Bodies (DLB)1
Not AvailableCompletedTreatmentAlzheimer's Disease (AD)1
Not AvailableCompletedTreatmentAlzheimer's Disease (AD) / Caregivers1
Not AvailableCompletedTreatmentAlzheimer's Disease (AD) / Dementias2
Not AvailableCompletedTreatmentMemory Disorders1
Not AvailableCompletedTreatmentModerate Alzheimer's Disease1
Not AvailableCompletedTreatmentParkinson's Disease (PD)1
Not AvailableCompletedTreatmentRett's Syndrome1
Not AvailableRecruitingNot AvailableAlzheimer's Disease (AD)1
Not AvailableTerminatedBasic ScienceAlzheimer's Disease (AD)1
Not AvailableTerminatedPreventionMemory Disturbances1
Not AvailableTerminatedTreatmentAlzheimer's Disease (AD) / Dementias1
Not AvailableUnknown StatusNot AvailableStrokes1

Pharmacoeconomics

Manufacturers
  • Eisai inc
  • Mutual pharmaceutical co inc
  • Teva pharmaceuticals usa inc
Packagers
  • Amerisource Health Services Corp.
  • AQ Pharmaceuticals Inc.
  • Bryant Ranch Prepack
  • Cardinal Health
  • DispenseXpress Inc.
  • Eisai Inc.
  • Greenstone LLC
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Resource Optimization and Innovation LLC
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
SolutionOral1 mg/1mL
TabletOral10 mg
TabletOral5 mg
Tablet, orally disintegratingOral10 mg
Tablet, orally disintegratingOral5 mg
TabletOral10 mg/1
TabletOral23 mg/1
TabletOral5 mg/1
Tablet, extended releaseOral23 mg/1
Tablet, film coatedOral10 mg/1
Tablet, film coatedOral23 mg/1
Tablet, film coatedOral5 mg/1
Tablet, orally disintegratingOral10 mg/1
Tablet, orally disintegratingOral5 mg/1
Capsule, extended releaseOral
CapsuleOral
KitOral
Prices
Unit descriptionCostUnit
Aricept ODT 30 5 mg Dispersible Tablet Box272.99USD box
Aricept 10 mg tablet10.93USD tablet
Aricept 5 mg tablet9.78USD tablet
Aricept odt 10 mg tablet8.03USD tablet
Aricept odt 5 mg tablet8.03USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US4895841No1990-01-232010-11-25Us
CA2252806No2005-11-222017-06-06Canada
CA1338808No1996-12-242013-12-24Canada
US7727548No2010-06-012022-06-23Us
US7727552No2010-06-012018-03-26Us
US8173708Yes2012-05-082026-05-22Us
US8283379Yes2012-10-092026-05-22Us
US8362085Yes2013-01-292026-05-22Us
US8039009Yes2011-10-182029-09-24Us
US8329752Yes2012-12-112026-05-22Us
US8598233Yes2013-12-032026-05-22Us
US8168209Yes2012-05-012026-05-22Us
US8481565No2013-07-092026-10-04Us
US8338486No2012-12-252025-11-22Us
US8058291No2011-11-152029-12-05Us
US8580858No2013-11-122025-11-22Us
US8338485No2012-12-252025-11-22Us
US8293794No2012-10-232025-11-22Us
US5061703Yes1991-10-292015-10-11Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)206.72 °CNot Available
water solubility2.931 mg/LNot Available
logP3.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0045 mg/mLALOGPS
logP4.14ALOGPS
logP4.21ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)17.02ChemAxon
pKa (Strongest Basic)8.62ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area38.77 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity112.11 m3·mol-1ChemAxon
Polarizability44.34 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9966
Blood Brain Barrier+0.9953
Caco-2 permeable+0.7742
P-glycoprotein substrateSubstrate0.7721
P-glycoprotein inhibitor IInhibitor0.7641
P-glycoprotein inhibitor IIInhibitor0.8202
Renal organic cation transporterInhibitor0.7696
CYP450 2C9 substrateNon-substrate0.8465
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7202
CYP450 1A2 substrateInhibitor0.5072
CYP450 2C9 inhibitorNon-inhibitor0.8189
CYP450 2D6 inhibitorInhibitor0.8684
CYP450 2C19 inhibitorNon-inhibitor0.8356
CYP450 3A4 inhibitorNon-inhibitor0.7411
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6138
Ames testNon AMES toxic0.6441
CarcinogenicityNon-carcinogens0.9528
BiodegradationNot ready biodegradable0.9145
Rat acute toxicity3.0123 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5386
hERG inhibition (predictor II)Inhibitor0.8095
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as n-benzylpiperidines. These are heterocyclic Compounds containing a piperidine ring conjugated to a benzyl group through one nitrogen ring atom.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Piperidines
Sub Class
Benzylpiperidines
Direct Parent
N-benzylpiperidines
Alternative Parents
Indanones / Phenylmethylamines / Benzylamines / Aryl alkyl ketones / Anisoles / Aralkylamines / Alkyl aryl ethers / Trialkylamines / Azacyclic compounds / Organopnictogen compounds
show 2 more
Substituents
N-benzylpiperidine / Indanone / Indane / Anisole / Benzylamine / Phenylmethylamine / Aryl ketone / Aryl alkyl ketone / Alkyl aryl ether / Aralkylamine
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, cyclic ketone (CHEBI:53289)

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Davis KL: Alzheimer's disease: seeking new ways to preserve brain function. Interview by Alice V. Luddington. Geriatrics. 1999 Feb;54(2):42-7; quiz 48. [PubMed:10024872]
  2. Kryger G, Silman I, Sussman JL: Structure of acetylcholinesterase complexed with E2020 (Aricept): implications for the design of new anti-Alzheimer drugs. Structure. 1999 Mar 15;7(3):297-307. [PubMed:10368299]
  3. Shepherd G, Klein-Schwartz W, Edwards R: Donepezil overdose: a tenfold dosing error. Ann Pharmacother. 1999 Jul-Aug;33(7-8):812-5. [PubMed:10466911]
  4. Kosasa T, Kuriya Y, Matsui K, Yamanishi Y: Effect of donepezil hydrochloride (E2020) on basal concentration of extracellular acetylcholine in the hippocampus of rats. Eur J Pharmacol. 1999 Sep 10;380(2-3):101-7. [PubMed:10513568]
  5. Jann MW: Rivastigmine, a new-generation cholinesterase inhibitor for the treatment of Alzheimer's disease. Pharmacotherapy. 2000 Jan;20(1):1-12. [PubMed:10641971]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  7. Sugimoto H: Donepezil hydrochloride: a treatment drug for Alzheimer's disease. Chem Rec. 2001;1(1):63-73. [PubMed:11893059]
  8. Ki YS, Park EY, Lee HW, Oh MS, Cho YW, Kwon YK, Moon JH, Lee KT: Donepezil, a potent acetylcholinesterase inhibitor, induces caspase-dependent apoptosis in human promyelocytic leukemia HL-60 cells. Biol Pharm Bull. 2010;33(6):1054-9. [PubMed:20522977]
  9. Repantis D, Laisney O, Heuser I: Acetylcholinesterase inhibitors and memantine for neuroenhancement in healthy individuals: a systematic review. Pharmacol Res. 2010 Jun;61(6):473-81. doi: 10.1016/j.phrs.2010.02.009. Epub 2010 Mar 1. [PubMed:20193764]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Hayslett RL, Tizabi Y: Effects of donepezil, nicotine and haloperidol on the central serotonergic system in mice: implications for Tourette's syndrome. Pharmacol Biochem Behav. 2005 Aug;81(4):879-86. [PubMed:16045972]
  2. Hayslett RL, Tizabi Y: Effects of donepezil on DOI-induced head twitch response in mice: implications for Tourette syndrome. Pharmacol Biochem Behav. 2003 Dec;76(3-4):409-15. [PubMed:14643839]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014]
  2. Lu J, Wan L, Zhong Y, Yu Q, Han Y, Chen P, Wang B, Li W, Miao Y, Guo C: Stereoselective metabolism of donepezil and steady-state plasma concentrations of S-donepezil based on CYP2D6 polymorphisms in the therapeutic responses of Han Chinese patients with Alzheimer's disease. J Pharmacol Sci. 2015 Nov;129(3):188-95. doi: 10.1016/j.jphs.2015.10.010. Epub 2015 Nov 5. [PubMed:26603528]

Drug created on June 13, 2005 07:24 / Updated on November 21, 2018 10:06