Identification

Name
Donepezil
Accession Number
DB00843
Description

In 2016, the global burden of dementia was estimated to be 43.8 million, demonstrating a significant increase from a global prevalence of 20.2 million in 1990.16 Donepezil, also known as Aricept, is a piperidine derivative acetylcholinesterase inhibitor used in the management of the dementia of Alzheimer's Disease, and in some cases, is used to manage other types of dementia.

Donepezil was first approved by the FDA in 1996, and its extended-release form was approved in combination with Memantine in 2014 to manage moderate and severe forms of Alzheimer's dementia.19,22 Though it does not alter the progression of Alzheimer's disease, donepezil is effective in managing the symptoms of its associated dementia.18

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 379.492
Monoisotopic: 379.214743799
Chemical Formula
C24H29NO3
Synonyms
  • Domepezil
  • Donepezil
  • Donepezilo
  • Donepezilum
External IDs
  • BNAG
  • E 2020

Pharmacology

Indication

Donepezil is indicated for the management of mild to moderate Alzheimer’s Disease at doses of 5 mg or 10 mg.19 It is also indicated for the management of moderate to severe Alzheimer’s Disease in a higher dose of 10 mg or 23 mg administered once daily.19 Off-label uses include the management of vascular dementia, Parkinson's Disease-associated dementia, and Lewy body dementia, among others.8,18 When combined with memantine, the extended-release form of donepezil is indicated to treat the symptoms of moderate to severe dementia.22

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

By inhibiting the acetylcholinesterase enzyme, donepezil improves the cognitive and behavioral signs and symptoms of Alzheimer's Disease, which may include apathy, aggression, confusion, and psychosis.8,15

Mechanism of action

The commonly accepted cholinergic hypothesis13 proposes that a portion of the cognitive and behavioral decline associated with Alzheimer's are the result of decreased cholinergic transmission in the central nervous system. Donepezil selectively and reversibly inhibits the acetylcholinesterase enzyme, which normally breaks down acetylcholine. The main pharmacological actions of this drug are believed to occur as the result of this enzyme inhibition, enhancing cholinergic transmission, which relieves the symptoms of Alzheimer's dementia. In addition to the above, other mechanisms of action of donepezil are possible, including the opposition of glutamate-induced excitatory transmission via downregulation of NMDA receptors and the regulation of amyloid proteins, which have demonstrated significant effects on the disease process of Alzheimer's.8,12,17 Other possible targets for donepezil may also include the inhibition various inflammatory signaling pathways, exerting neuroprotective effects.10,14

TargetActionsOrganism
AAcetylcholinesterase
inhibitor
Humans
U5-hydroxytryptamine receptor 2A
inducer
Humans
UCholinesterase
inducer
Humans
UNitric oxide synthase, brain
inhibitor
inducer
Humans
UTumor necrosis factor-inducible gene 6 protein
inhibitor
Humans
UInterleukin-1 beta
inhibitor
inducer
Humans
UNuclear factor NF-kappa-B
inhibitor
Humans
UNMDA receptor
downregulator
Humans
Absorption

Donepezil is slowly absorbed via the gastrointestinal tract after oral administration. Tmax is 3 to 4 hours with a bioavailability of 100% and steady-state concentrations are attained within 15 to 21 days of administration.8 The Tmax in one pharmacokinetic study determined a Tmax of 4.1 ± 1.5 hours.6 The Cmax of 5 mg donepezil tablets is estimated to be 8.34 ng/mL, according to the Canadian monograph.23 The AUC of 5 mg donepezil tablets has been determined to be 221.90-225.36 ng.hr/mL.23

Volume of distribution

The volume of distribution of donepezil is 11.8 ± 1.7 L/kg for a 5-mg dose and 11.6 ± 1.91 L/kg for a 10-mg dose. It is largely distributed in the extravascular compartments. Donepezil crosses the blood-brain barrier and cerebrospinal fluid concentrations at the above doses have been measured at 15.7%.8 The volume of distribution at steady-state according to the FDA label for donepezil ranges from 12 - 16 L/kg.19

Protein binding

Donepezil is 96% protein-bound, with approximately 75% binding to albumin and approximately 21% binding to alpha-1-glycoprotein.8,23

Metabolism

Donepezil is metabolized by first pass metabolism in the liver, primarily by CYP3A4, in addition to CYP2D6. After this, O-dealkylation, hydroxylation, N-oxidation, hydrolysis, and O-glucuronidation occur, producing various metabolites with similar half-lives to the unchanged parent drug. A study of the pharmacokinetics of radiolabeled donepezil demonstrated that about 53% of plasma radioactivity appeared as donepezil in the unchanged form, and 11% was identified as the metabolite 6-O-desmethyl donepezil, which exerts similar potency inhibition of the acetylcholinesterase enzyme.8,19 This drug is heavily metabolized to four primary metabolites, two of which are considered pharmacologically active, as well as to multiple inactive and unidentified metabolites.19

Hover over products below to view reaction partners

Route of elimination

In a study of radiolabeled administration donepezil in healthy adults, 57% of measured radioactivity was identified in the urine, and 5% was identified in the feces.8

Half-life

The average elimination half-life of donepezil is about 70 hours according to the results of various studies and the FDA label for donepezil.8,19. One pharmacokinetic study determined the average terminal half-life to be 81.5±22.0 h6

Clearance

According to the FDA label, the average apparent plasma clearance of this drug is 0.13 – 0.19 L/hr/kg.19 A 5 mg dose of donepezil in healthy patients was shown to have a plasma clearance of 0.110±0.02 L/h/kg.23 In 10 patients diagnosed with alcoholic cirrhosis, showed a mean decrease in clearance by 20% when compared to the clearance in 10 healthy subjects. In 4 patients with severe renal impairment compared to 4 healthy subjects, no significant change in clearance was noted.23

Adverse Effects
Learn about our commercial Adverse Effects data.
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Toxicity

LD50

The rat oral LD50 of donepezil is 32.6 mg/kg.21

Overdose information

Signs and symptoms of overdose with cholinesterase inhibitors such as donepezil can include severe nausea and vomiting, bradycardia, hypotension, perspiration, seizures, muscle weakness respiratory depression, and collapse. Significant muscle weakness may result in death if the respiratory muscles are affected by donepezil overdose. To manage an overdose, anticholinergics can be employed as antidotes. Atropine at intravenous doses of 1.0 - 2.0 mg can be administered and titrated according to the clinical response. Consult the local poison control center for the most updated guidelines on the management of a donepezil overdose. Whether donepezil can be removed from the body with dialysis is unknown at this time.19

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
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Donepezil can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Donepezil can be increased when combined with Abatacept.
AbemaciclibAbemaciclib may decrease the excretion rate of Donepezil which could result in a higher serum level.
AbirateroneThe metabolism of Donepezil can be decreased when combined with Abiraterone.
AcebutololThe metabolism of Donepezil can be decreased when combined with Acebutolol.
AcenocoumarolThe metabolism of Acenocoumarol can be decreased when combined with Donepezil.
AcetaminophenThe metabolism of Donepezil can be decreased when combined with Acetaminophen.
AcetazolamideThe risk or severity of adverse effects can be increased when Acetazolamide is combined with Donepezil.
AcetohexamideThe metabolism of Donepezil can be decreased when combined with Acetohexamide.
AcetophenazineThe risk or severity of adverse effects can be increased when Donepezil is combined with Acetophenazine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid alcohol.
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Donepezil hydrochloride3O2T2PJ89D120011-70-3XWAIAVWHZJNZQQ-UHFFFAOYSA-N
Product Images
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)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act DonepezilTabletOralActavis Pharma Company2013-12-272018-06-12Canada flag
Act DonepezilTabletOralActavis Pharma Company2013-12-272018-06-12Canada flag
Act Donepezil ODTTablet, orally disintegratingOralTEVA Canada Limited2013-12-27Not applicableCanada flag
Act Donepezil ODTTablet, orally disintegratingOralTEVA Canada Limited2013-12-27Not applicableCanada flag
AriceptTablet, film coated10 mg/1OralCardinal Health1996-11-262014-11-30US flag
AriceptTablet, film coated23 mg/1OralAvera McKennan Hospital2015-03-232017-05-24US flag
AriceptTablet, film coated23 mg/1OralEisai Inc.2010-07-23Not applicableUS flag62856 0247 90 nlmimage10 c412e257
AriceptTablet, film coated5 mg/1OralPhysicians Total Care, Inc.2008-05-09Not applicableUS flag
AriceptTablet5 mgOralPfizer Canada Ulc1997-08-20Not applicableCanada flag
AriceptTablet, film coated10 mg/1OralPD-Rx Pharmaceuticals, Inc.1996-11-25Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-donepezilTabletOralAccel Pharma Inc2014-09-042019-10-28Canada flag
Accel-donepezilTabletOralAccel Pharma Inc2014-09-042019-10-28Canada flag
Ag-donepezilTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Ag-donepezilTabletOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-donepezilTabletOralApotex Corporation2014-12-27Not applicableCanada flag
Apo-donepezilTabletOralApotex Corporation2013-12-27Not applicableCanada flag
Auro-donepezilTabletOralAuro Pharma Inc2013-12-27Not applicableCanada flag
Auro-donepezilTabletOralAuro Pharma Inc2013-12-27Not applicableCanada flag
Bio-donepezilTabletOralBiomed Pharma2013-12-27Not applicableCanada flag
Bio-donepezilTabletOralBiomed Pharma2013-12-27Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (7 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals NY LLC2017-02-01Not applicableUS flag
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (28 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals NY LLC2017-02-01Not applicableUS flag
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (21 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals NY LLC2017-02-01Not applicableUS flag
Memantine and Donepezil Hydrochlorides Extended-releaseDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (14 mg/1)Capsule, extended releaseOralAmneal Pharmaceuticals NY LLC2017-02-01Not applicableUS flag
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)KitOralAllergan, Inc.2016-11-28Not applicableUS flag
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)KitOralAllergan, Inc.2016-11-28Not applicableUS flag
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (28 mg/1)CapsuleOralAllergan, Inc.2014-12-24Not applicableUS flag
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)KitOralAllergan, Inc.2016-11-28Not applicableUS flag
NamzaricDonepezil hydrochloride (10 mg/1) + Memantine hydrochloride (21 mg/1)CapsuleOralAllergan, Inc.2016-07-18Not applicableUS flag
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)KitOralAllergan, Inc.2016-11-28Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Donepezil HydrochlorideDonepezil hydrochloride (10 mg/1)Tablet, film coatedOralTeva2011-04-142011-04-14US flag
Donepezil HydrochlorideDonepezil hydrochloride (5 mg/1)Tablet, film coatedOralTeva2011-04-142011-04-14US flag

Categories

ATC Codes
N06DA52 — Donepezil and memantineN06DA53 — Donepezil, memantine and ginkgo foliumN06DA02 — Donepezil
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic heteropolycyclic compound / Aryl alkyl ketone / Aryl ketone / Azacycle / Benzenoid / Benzylamine
show 16 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
piperidines, cyclic ketone (CHEBI:53289)

Chemical Identifiers

UNII
8SSC91326P
CAS number
120014-06-4
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

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]
  4. Korabecny J, Spilovska K, Mezeiova E, Benek O, Juza R, Kaping D, Soukup O: A systematic review on donepezil-based derivatives as potential cholinesterase inhibitors for Alzheimer's disease. Curr Med Chem. 2018 May 16. pii: CMC-EPUB-90497. doi: 10.2174/0929867325666180517094023. [PubMed:29768996]
  5. Prvulovic D, Schneider B: Pharmacokinetic and pharmacodynamic evaluation of donepezil for the treatment of Alzheimer's disease. Expert Opin Drug Metab Toxicol. 2014 Jul;10(7):1039-50. doi: 10.1517/17425255.2014.915028. Epub 2014 Apr 30. [PubMed:24785550]
  6. Rogers SL, Friedhoff LT: Pharmacokinetic and pharmacodynamic profile of donepezil HCl following single oral doses. Br J Clin Pharmacol. 1998 Nov;46 Suppl 1:1-6. doi: 10.1046/j.1365-2125.1998.0460s1001.x. [PubMed:9839758]
  7. Tiseo PJ, Perdomo CA, Friedhoff LT: Metabolism and elimination of 14C-donepezil in healthy volunteers: a single-dose study. Br J Clin Pharmacol. 1998 Nov;46 Suppl 1:19-24. doi: 10.1046/j.1365-2125.1998.0460s1019.x. [PubMed:9839761]
  8. Seltzer B: Donepezil: a review. Expert Opin Drug Metab Toxicol. 2005 Oct;1(3):527-36. doi: 10.1517/17425255.1.3.527 . [PubMed:16863459]
  9. Hughes RE, Nikolic K, Ramsay RR: One for All? Hitting Multiple Alzheimer's Disease Targets with One Drug. Front Neurosci. 2016 Apr 25;10:177. doi: 10.3389/fnins.2016.00177. eCollection 2016. [PubMed:27199640]
  10. Hwang J, Hwang H, Lee HW, Suk K: Microglia signaling as a target of donepezil. Neuropharmacology. 2010 Jun;58(7):1122-9. doi: 10.1016/j.neuropharm.2010.02.003. Epub 2010 Feb 11. [PubMed:20153342]
  11. Owen RT: Memantine and donepezil: a fixed drug combination for the treatment of moderate to severe Alzheimer's dementia. Drugs Today (Barc). 2016 Apr;52(4):239-48. doi: 10.1358/dot.2016.52.4.2479357. [PubMed:27252988]
  12. Murphy MP, LeVine H 3rd: Alzheimer's disease and the amyloid-beta peptide. J Alzheimers Dis. 2010;19(1):311-23. doi: 10.3233/JAD-2010-1221. [PubMed:20061647]
  13. Terry AV Jr, Buccafusco JJ: The cholinergic hypothesis of age and Alzheimer's disease-related cognitive deficits: recent challenges and their implications for novel drug development. J Pharmacol Exp Ther. 2003 Sep;306(3):821-7. doi: 10.1124/jpet.102.041616. Epub 2003 Jun 12. [PubMed:12805474]
  14. Srinivasan M, Lahiri DK: Significance of NF-kappaB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis. Expert Opin Ther Targets. 2015 Apr;19(4):471-87. doi: 10.1517/14728222.2014.989834. Epub 2015 Feb 4. [PubMed:25652642]
  15. Li XL, Hu N, Tan MS, Yu JT, Tan L: Behavioral and psychological symptoms in Alzheimer's disease. Biomed Res Int. 2014;2014:927804. doi: 10.1155/2014/927804. Epub 2014 Jul 15. [PubMed:25133184]
  16. Authors unspecified: Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol. 2019 Jan;18(1):88-106. doi: 10.1016/S1474-4422(18)30403-4. Epub 2018 Nov 26. [PubMed:30497964]
  17. Shen H, Kihara T, Hongo H, Wu X, Kem WR, Shimohama S, Akaike A, Niidome T, Sugimoto H: Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of alpha7 nicotinic receptors and internalization of NMDA receptors. Br J Pharmacol. 2010 Sep;161(1):127-39. doi: 10.1111/j.1476-5381.2010.00894.x. [PubMed:20718745]
  18. Anil Kumar; Sandeep Sharma (2019). Donepezil. Stat Pearls.
  19. Donepezil FDA label [Link]
  20. Australian monograph, Donepezil [Link]
  21. Pfizer MSDS, Donepezil hydrochloride [Link]
  22. FDA label, Namzaric [Link]
  23. Pfizer monograph, donepezil [Link]
Human Metabolome Database
HMDB0005041
KEGG Drug
D00670
PubChem Compound
3152
PubChem Substance
46504803
ChemSpider
3040
BindingDB
8960
RxNav
135447
ChEBI
53289
ChEMBL
CHEMBL502
Therapeutic Targets Database
DAP000560
PharmGKB
PA449394
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Donepezil
AHFS Codes
  • 12:04.00 — Parasympathomemetic (Cholinergic) Agents
MSDS
Download (58.2 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingOtherAlzheimer's Disease (AD)1
4Active Not RecruitingTreatmentAlzheimer's Disease (AD) / Cognitive Change1
4CompletedBasic ScienceAmblyopia1
4CompletedBasic ScienceSleep Deprivation1
4CompletedPreventionAlzheimer's Disease (AD) / Delirium, Dementia, Amnestic, Cognitive Disorders / Mild Cognitive Impairment (MCI)1
4CompletedPreventionCognition Disorders1
4CompletedPreventionCognitively Normal Elderly Individuals1
4CompletedPreventionDelirium / Postoperative Complications2
4CompletedSupportive CareGeriatrics / Mental Health1
4CompletedTreatmentAlzheimer's Disease (AD)7

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
Tablet, film coated10 mg
Tablet, film coated5 mg
Tablet5 mg
SolutionOral1 mg/1mL
Tablet10 MG
Tablet, coated10 mg
Tablet, film coatedOral10 MG
Tablet, film coatedOral5 MG
Tablet, orally disintegratingOral
TabletOral5 mg
Tablet, film coatedOral90 mg
Tablet
Tablet, film coated, extended release10 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
Tablet, coated5 mg
Tablet, effervescentOral10 mg
Tablet, effervescentOral5 mg
Tablet, coatedOral10 mg
Capsule, extended releaseOral
CapsuleOral
KitOral
Tablet, coatedOral5 mg
TabletOral
TabletOral10 mg
Tablet, effervescent10 mg
Tablet, effervescent5 mg
Tablet, coated90 mg
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)Region
US4895841No1990-01-232010-11-25US flag
CA2252806No2005-11-222017-06-06Canada flag
CA1338808No1996-12-242013-12-24Canada flag
US7727548No2010-06-012022-06-23US flag
US7727552No2010-06-012018-03-26US flag
US8173708Yes2012-05-082026-05-22US flag
US8283379Yes2012-10-092026-05-22US flag
US8362085Yes2013-01-292026-05-22US flag
US8039009Yes2011-10-182029-09-24US flag
US8329752Yes2012-12-112026-05-22US flag
US8598233Yes2013-12-032026-05-22US flag
US8168209Yes2012-05-012026-05-22US flag
US8481565No2013-07-092026-10-04US flag
US8338486No2012-12-252025-11-22US flag
US8058291No2011-11-152029-12-05US flag
US8580858No2013-11-122025-11-22US flag
US8338485No2012-12-252025-11-22US flag
US8293794No2012-10-232025-11-22US flag
US5061703Yes1991-10-292015-10-11US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)223-227https://aksci.com/item_detail.php?cat=J10827
boiling point (°C)527.9https://www.lookchem.com/Donepezil-hydrochloride/
water solubility31mg/mLhttps://aksci.com/item_detail.php?cat=J10827
logP4.7https://www.sunpharma.com/australia-pi-download/50508/Donepezil
pKa8.9https://www.sunpharma.com/australia-pi-download/50508/Donepezil
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

Targets

Details
1. Acetylcholinesterase
Kind
Protein
Organism
Humans
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]
  10. Donepezil FDA label [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
This is a potential target of donepezil.
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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
Curator comments
This is a potential target, based on data from in vitro studies.
General Function
Identical protein binding
Specific Function
Esterase with broad substrate specificity. Contributes to the inactivation of the neurotransmitter acetylcholine. Can degrade neurotoxic organophosphate esters.
Gene Name
BCHE
Uniprot ID
P06276
Uniprot Name
Cholinesterase
Molecular Weight
68417.575 Da
References
  1. Seltzer B: Donepezil: a review. Expert Opin Drug Metab Toxicol. 2005 Oct;1(3):527-36. doi: 10.1517/17425255.1.3.527 . [PubMed:16863459]
  2. Liston DR, Nielsen JA, Villalobos A, Chapin D, Jones SB, Hubbard ST, Shalaby IA, Ramirez A, Nason D, White WF: Pharmacology of selective acetylcholinesterase inhibitors: implications for use in Alzheimer's disease. Eur J Pharmacol. 2004 Feb 13;486(1):9-17. doi: 10.1016/j.ejphar.2003.11.080. [PubMed:14751402]
  3. Nordberg A, Ballard C, Bullock R, Darreh-Shori T, Somogyi M: A review of butyrylcholinesterase as a therapeutic target in the treatment of Alzheimer's disease. Prim Care Companion CNS Disord. 2013;15(2). pii: 12r01412. doi: 10.4088/PCC.12r01412. Epub 2013 Mar 7. [PubMed:23930233]
  4. Ogura H, Kosasa T, Kuriya Y, Yamanishi Y: Comparison of inhibitory activities of donepezil and other cholinesterase inhibitors on acetylcholinesterase and butyrylcholinesterase in vitro. Methods Find Exp Clin Pharmacol. 2000 Oct;22(8):609-13. [PubMed:11256231]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
Curator comments
This target action is likely mediated via donepezil's effect on microglial cells.
General Function
Tetrahydrobiopterin binding
Specific Function
Produces nitric oxide (NO) which is a messenger molecule with diverse functions throughout the body. In the brain and peripheral nervous system, NO displays many properties of a neurotransmitter. P...
Gene Name
NOS1
Uniprot ID
P29475
Uniprot Name
Nitric oxide synthase, brain
Molecular Weight
160969.095 Da
References
  1. Hwang J, Hwang H, Lee HW, Suk K: Microglia signaling as a target of donepezil. Neuropharmacology. 2010 Jun;58(7):1122-9. doi: 10.1016/j.neuropharm.2010.02.003. Epub 2010 Feb 11. [PubMed:20153342]
  2. Nakahata K, Kinoshita H, Hama-Tomioka K, Ishida Y, Matsuda N, Hatakeyama N, Haba M, Kondo T, Hatano Y: Cholinesterase inhibitor donepezil dilates cerebral parenchymal arterioles via the activation of neuronal nitric oxide synthase. Anesthesiology. 2008 Jul;109(1):124-9. doi: 10.1097/ALN.0b013e31817c0316. [PubMed:18580182]
  3. Haraguchi Y, Mizoguchi Y, Ohgidani M, Imamura Y, Murakawa-Hirachi T, Nabeta H, Tateishi H, Kato TA, Monji A: Donepezil suppresses intracellular Ca(2+) mobilization through the PI3K pathway in rodent microglia. J Neuroinflammation. 2017 Dec 22;14(1):258. doi: 10.1186/s12974-017-1033-0. [PubMed:29273047]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Hyaluronic acid binding
Specific Function
Possibly involved in cell-cell and cell-matrix interactions during inflammation and tumorigenesis.
Gene Name
TNFAIP6
Uniprot ID
P98066
Uniprot Name
Tumor necrosis factor-inducible gene 6 protein
Molecular Weight
31203.09 Da
References
  1. Hwang J, Hwang H, Lee HW, Suk K: Microglia signaling as a target of donepezil. Neuropharmacology. 2010 Jun;58(7):1122-9. doi: 10.1016/j.neuropharm.2010.02.003. Epub 2010 Feb 11. [PubMed:20153342]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Protein domain specific binding
Specific Function
Potent proinflammatory cytokine. Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, ...
Gene Name
IL1B
Uniprot ID
P01584
Uniprot Name
Interleukin-1 beta
Molecular Weight
30747.7 Da
References
  1. Hwang J, Hwang H, Lee HW, Suk K: Microglia signaling as a target of donepezil. Neuropharmacology. 2010 Jun;58(7):1122-9. doi: 10.1016/j.neuropharm.2010.02.003. Epub 2010 Feb 11. [PubMed:20153342]
  2. Reale M, Iarlori C, Gambi F, Lucci I, Salvatore M, Gambi D: Acetylcholinesterase inhibitors effects on oncostatin-M, interleukin-1 beta and interleukin-6 release from lymphocytes of Alzheimer's disease patients. Exp Gerontol. 2005 Mar;40(3):165-71. doi: 10.1016/j.exger.2004.12.003. Epub 2005 Jan 8. [PubMed:15763393]
  3. Zhang T, Tian F, Wang J, Zhou S, Dong X, Guo K, Jing J, Zhou Y, Chen Y: Donepezil attenuates high glucose-accelerated senescence in human umbilical vein endothelial cells through SIRT1 activation. Cell Stress Chaperones. 2015 Sep;20(5):787-92. doi: 10.1007/s12192-015-0601-4. Epub 2015 Jul 21. [PubMed:26194321]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transcriptional activator activity, rna polymerase ii core promoter proximal region sequence-specific binding
Specific Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related...

Components:
References
  1. Kim HG, Moon M, Choi JG, Park G, Kim AJ, Hur J, Lee KT, Oh MS: Donepezil inhibits the amyloid-beta oligomer-induced microglial activation in vitro and in vivo. Neurotoxicology. 2014 Jan;40:23-32. doi: 10.1016/j.neuro.2013.10.004. Epub 2013 Nov 1. [PubMed:24189446]
  2. Srinivasan M, Lahiri DK: Significance of NF-kappaB as a pivotal therapeutic target in the neurodegenerative pathologies of Alzheimer's disease and multiple sclerosis. Expert Opin Ther Targets. 2015 Apr;19(4):471-87. doi: 10.1517/14728222.2014.989834. Epub 2015 Feb 4. [PubMed:25652642]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Downregulator
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Shen H, Kihara T, Hongo H, Wu X, Kem WR, Shimohama S, Akaike A, Niidome T, Sugimoto H: Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of alpha7 nicotinic receptors and internalization of NMDA receptors. Br J Pharmacol. 2010 Sep;161(1):127-39. doi: 10.1111/j.1476-5381.2010.00894.x. [PubMed:20718745]

Enzymes

Kind
Protein
Organism
Humans
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. Coin A, Pamio MV, Alexopoulos C, Granziera S, Groppa F, de Rosa G, Girardi A, Sergi G, Manzato E, Padrini R: Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease. Eur J Clin Pharmacol. 2016 Jun;72(6):711-7. doi: 10.1007/s00228-016-2033-1. Epub 2016 Mar 8. [PubMed:26952092]
  3. Anil Kumar; Sandeep Sharma (2019). Donepezil. Stat Pearls.
  4. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
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. Coin A, Pamio MV, Alexopoulos C, Granziera S, Groppa F, de Rosa G, Girardi A, Sergi G, Manzato E, Padrini R: Donepezil plasma concentrations, CYP2D6 and CYP3A4 phenotypes, and cognitive outcome in Alzheimer's disease. Eur J Clin Pharmacol. 2016 Jun;72(6):711-7. doi: 10.1007/s00228-016-2033-1. Epub 2016 Mar 8. [PubMed:26952092]
  3. Anil Kumar; Sandeep Sharma (2019). Donepezil. Stat Pearls.
Kind
Protein
Organism
Humans
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]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. Takeuchi R, Shinozaki K, Nakanishi T, Tamai I: Local Drug-Drug Interaction of Donepezil with Cilostazol at Breast Cancer Resistance Protein (ABCG2) Increases Drug Accumulation in Heart. Drug Metab Dispos. 2016 Jan;44(1):68-74. doi: 10.1124/dmd.115.066654. Epub 2015 Oct 14. [PubMed:26467765]

Drug created on June 13, 2005 07:24 / Updated on September 20, 2020 08:50

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