Cited by 108Cholinesterase and Neurodegenerative DiseasesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

The DOI matches its Crossref record.

Donepezil: an anticholinesterase inhibitor for Alzheimer’s disease

Shintani, Ellen Y., Uchida, Kathryn M.·1997·American Journal of Health-System Pharmacy

DOI 10.1093/ajhp/54.24.2805

Open this paper in CoChat — free account

Abstract

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug interactions, and dosage and administration of donepezil are reviewed. Donepezil is a synthetic noncovalent reversible inhibitor of acetylcholinesterase (AChE) for the treatment of mild to moderate dementia associated with Alzheimer's disease. In contrast to tacrine hydrochloride, the only comparable agent currently approved by FDA, donepezil exhibits a relatively high degree of selectivity for neuronal AChE as opposed to butyrylcholinesterase. It has a half-life of 60 hours in young adults and 104 hours in elderly patients. In clinical trials, donepezil has been associated with significant improvements in Alzheimer's Disease Assessment Scale-cognitive subscale and Clinical Interview-Based Impression of Change scores. The most common adverse effects associated with donepezil are nausea, diarrhea, anorexia, and vomiting, which are most likely to occur during dose initiation or adjustment. Hepatotoxicity, a dose-limiting adverse effect that sometimes requires discontinuation of tacrine, has not been reported with donepezil. Donepezil does not appear to interact with theophylline, cimetidine, warfarin, or digoxin. Ketoconazole and quinidine inhibit the metabolism of donepezil in vitro, but there is a lack of clinical data showing that these drugs decrease the clearance of donepezil. The initial recommended dosage is 5 mg daily before bedtime, with a dosage increase to 10 mg after four to six weeks according to the patient's response and tolerance. Donepezil appears to be preferable to tacrine as the initial agent for patients with mild to moderate dementia associated with Alzheimer's disease.

Integrity signals

Registry

Crossref · 10.1093/ajhp/54.24.2805

Cites

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Sorted by citations

Clinical pharmacokinetics and pharmacodynamics of cholinesterase inhibitors
Jann, M. W., Shirley, K. L., & Small, G. W. (2002) · Clinical Pharmacokinetics · doi:10.2165/00003088-200241100-00003 · Cited by 365
Pharmacologic treatments of dementia
Bonner, L. T., & Peskind, E. R. (2002) · Medical Clinics of North America · doi:10.1016/s0025-7125(02)00007-x · Cited by 226
Pharmacodynamic, Pharmacokinetic and Pharmacogenetic Aspects of Drugs Used in the Treatment of Alzheimer’s Disease
Noetzli, M., & Eap, C. B. (2013) · Clinical Pharmacokinetics · doi:10.1007/s40262-013-0038-9 · Cited by 230
“In human plasma, M1 is only present at about 20 % of the concentration of the parent drug [64].”
Background
Effectiveness and tolerability of high-dose (23 mg/d) versus standard-dose (10 mg/d) donepezil in moderate to severe Alzheimer's disease: A 24-week, randomized, double-blind study
Farlow, M. R., Salloway, S., Tariot, P. N., Yardley, J., Moline, M. L., Wang, Q., Brand‐Schieber, E., Zou, H., Hsu, T., & Satlin, A. (2010) · Clinical Therapeutics · doi:10.1016/j.clinthera.2010.06.019 · Cited by 214
Melatonin Rescue Oxidative Stress-Mediated Neuroinflammation/ Neurodegeneration and Memory Impairment in Scopolamine-Induced Amnesia Mice Model
Muhammad, T., Ali, T., Ikram, M. A., Khan, A., Alam, S. I., & Kim, M. O. (2018) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-018-9824-3 · Cited by 201
Donepezil
Dooley, M., & Lamb, H. M. (2000) · Drugs & Aging · doi:10.2165/00002512-200016030-00005 · Cited by 192
“[7] It is a progressive, neurodegenerative neurological disease which usually occurs in later life, although it may sometimes present in younger people.”
Background
Recent advances in colorimetric strategies for acetylcholinesterase assay and their applications
Liu, D., Xu, B., & Chen, D. (2021) · TrAC Trends in Analytical Chemistry · doi:10.1016/j.trac.2021.116320 · Cited by 154
Tip-loaded dissolving microneedles for transdermal delivery of donepezil hydrochloride for treatment of Alzheimer’s disease
Kim, J., Han, M.-R., Kim, Y., Shin, S.-W., Nam, S.-Y., & Park, J. (2016) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2016.06.006 · Cited by 153
“Different classes of AchE inhibitors, including tacrine, donepezil, rivastigmine, galantamine, xanthostigmine, para-aminobenzoic acid, coumarin, flavonoid, and pyrrolo-isoxazole analogs, have hydrochloride (DPH) is the second FDA-approved anti-AD drug and is considered a safe and well-tolerated drug for AD patients [7…”
Background
Alzheimer's disease
Schachter, A. S., & Davis, K. L. (2000) · Dialogues in Clinical Neuroscience · doi:10.31887/dcns.2000.2.2/asschachter · Cited by 153
Donepezil: a review
Seltzer, B. (2005) · Expert Opinion on Drug Metabolism & Toxicology · doi:10.1517/17425255.1.3.527 · Cited by 134
“3 Effects of other drugs on the metabolism of donepezil Ketoconazole and quinidine, which are inhibitors of CYP3A4 and -2D6, respectively, have been shown to inhibit donepezil’s metabolism in vitro [61].”
Background
Inappropriate Medication Prescribing in Residential Care/Assisted Living Facilities
Sloane, P. D., Zimmerman, S. I., Brown, L. C., et al. (2002) · Journal of the American Geriatrics Society · doi:10.1046/j.1532-5415.2002.50253.x · Cited by 116
Indian Medicinal Herbs and Formulations for Alzheimer’s Disease, from Traditional Knowledge to Scientific Assessment
Mehla, J., Gupta, P., Pahuja, M., Diwan, D., & Diksha, D. (2020) · Brain Sciences · doi:10.3390/brainsci10120964 · Cited by 108
Possible Causes of Alzheimer's Disease: Amyloid Fragments, Free Radicals, and Calcium Homeostasis
Hölscher, C. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0193 · Cited by 106
“…system, such as the acetylcholine esterase inhibitors Tacrine, Velnacrine, or Aricept, since it was believed until recently that the main cause for AD is a degeneration of basal brain nuclei that use acetylcholine as a neurotransmitter (Gooch and Stennett, 1996; Shintani and Uchida, 1997).”
Background
Donepezil dose-dependently inhibits acetylcholinesterase activity in various areas and in the presynaptic cholinergic and the postsynaptic cholinoceptive enzyme-positive structures in the human and rat brain
Kása, P., Papp, H., Kása, P., & Torok, I. (2000) · Neuroscience · doi:10.1016/s0306-4522(00)00335-3 · Cited by 88
Classics in Chemical Neuroscience: Donepezil
Brewster, J. T., Dell’Acqua, S., Thach, D. Q., & Sessler, J. L. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00517 · Cited by 94
Donepezil in treatment-resistant bipolar disorder
Burt, T., Sachs, G. S., & Demopulos, C. M. (1999) · Biological Psychiatry · doi:10.1016/s0006-3223(98)00320-5 · Cited by 77
Spectroscopic, calorimetric and molecular docking insight into the interaction of Alzheimer’s drug donepezil with human transferrin: implications of Alzheimer’s drug
Shamsi, A., Shahwan, M. J., Ahamad, S., Hassan, M. I., Ahmad, F., & Islam, A. (2019) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2019.1595728 · Cited by 77
Probing the interaction of Rivastigmine Tartrate, an important Alzheimer’s drug, with serum albumin: Attempting treatment of Alzheimer’s disease
Shamsi, A., Mohammad, T., Anwar, S., Alajmi, M. F., Hussain, A., Hassan, M. I., Ahmad, F., & Islam, A. (2020) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2020.01.134 · Cited by 73
Bingo vs. physical intervention in stimulating short-term cognition in Alzheimer's disease patients
Sobel, B. P. (2001) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/153331750101600214 · Cited by 66
Akebia Saponin D attenuates amyloid β-induced cognitive deficits and inflammatory response in rats: Involvement of Akt/NF-κB pathway
Yu, X., Wang, L., Du, Q., Ma, L., Chen, L., You, R., Liu, L., Ling, J., Yang, Z., & Ji, H. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.07.045 · Cited by 66
Molecular modeling, docking and ADMET studies applied to the design of a novel hybrid for treatment of Alzheimer's disease
da Silva, C. H. T. D. P., Campo, V. L., Carvalho, I., et al. (2006) · Journal of Molecular Graphics and Modelling · doi:10.1016/j.jmgm.2005.12.002 · Cited by 63
Donepezil Overdose: A Tenfold Dosing Error
Shepherd, G., Klein‐Schwartz, W., & Edwards, R. (1999) · Annals of Pharmacotherapy · doi:10.1345/aph.18273 · Cited by 62
Sustained improvements in patients with dementia of Alzheimer's type (DAT) 6 months after termination of Cerebrolysin therapy
Rüther, E., Ritter, R., Apecechea, M., Freytag, S., Gmeinbauer, R., & Windisch, M. (2000) · Journal of Neural Transmission · doi:10.1007/s007020070061 · Cited by 55
Population pharmacokinetic approach to evaluate the effect of CYP2D6 , CYP3A , ABCB1 , POR and NR1I2 genotypes on donepezil clearance
Noetzli, M., Guidi, M., Ebbing, K., et al. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12325 · Cited by 54
Donepezil for Alzheimer’s disease
Benjamin, B., & Burns, A. S. (2007) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.7.10.1243 · Cited by 55
miRNAs as Therapeutic Tools in Alzheimer’s Disease
Lee, C. Y., Ryu, I. S., Ryu, J., & Cho, H. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222313012 · Cited by 53
“Donepezil was approved by the FDA in 1996, and its side effects include nausea, difficulty sleeping, abnormal heart rhythms, and seizures [37].”
Background
Causes of Syncope in Patients with Alzheimer???s Disease Treated with Donepezil
Bordier, P., Lanusse, S., Garrigue, S., Reynard, C., Robert, F., Gencel, L., & Lafitte, A. (2005) · Drugs & Aging · doi:10.2165/00002512-200522080-00005 · Cited by 50
Cardiac Safety of Donepezil in Elderly Patients with Alzheimer Disease
Işık, A. T., Yıldız, G. B., Bozoğlu, E., et al. (2012) · Internal Medicine · doi:10.2169/internalmedicine.51.6671 · Cited by 44
“Cholinesterase inhibitors (ChEIs) are currently considered to be the first line treatment for AD (2).”
Background
Donepezil (Aricept®) for treatment of Alzheimer´s disease and other dementing conditions
Geldmacher, D. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.1.5 · Cited by 45
Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer’s disease
Muolokwu, C. E., Chaulagain, B., Gothwal, A., Mahanta, A. K., Tagoe, B., Lamsal, B., & Singh, J. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1405423 · Cited by 42
“Its associated side effects include sleep disturbances, irregular heart rhythms, seizures, and nausea (Shintani and Uchida, 1997).”
Background
Cardiovascular Effects and Risk of Syncope Related to Donepezil in Patients with Alzheimer???s Disease
Bordier, P., Garrigue, S., Lanusse, S., Margaine, J., Robert, F., Gencel, L., & Lafitte, A. (2006) · CNS Drugs · doi:10.2165/00023210-200620050-00005 · Cited by 41
Sea Cucumber-Derived Peptide Attenuates Scopolamine-Induced Cognitive Impairment by Preventing Hippocampal Cholinergic Dysfunction and Neuronal Cell Death
Zhao, Y., Lu, Z., Xu, X., Sun, N., & Lin, S. (2022) · Journal of Agricultural and Food Chemistry · doi:10.1021/acs.jafc.1c07232 · Cited by 43
Significance of syncope in patients with Alzheimer's disease treated with cholinesterase inhibitors
Bordier, P. (2003) · EP Europace · doi:10.1016/s1099-5129(03)00080-1 · Cited by 39
“Cholinesterase inhibitors are used to treat Alzheimer’s disease but their cholinergic side-effects may result in discontinuation of therapy([5,6]).”
Background
Swertisin, a C-glucosylflavone, ameliorates scopolamine-induced memory impairment in mice with its adenosine A1 receptor antagonistic property
Lee, H. E., Jeon, S. J., Ryu, B., Park, S. J., Ko, S. Y., Lee, Y., Kim, E., Lee, S. H., Kim, H., Jang, D. S., et al. (2016) · Behavioural Brain Research · doi:10.1016/j.bbr.2016.03.030 · Cited by 38
Fulminant Chemical Hepatitis Possibly Associated with Donepezil and Sertraline Therapy
Verrico, M. M., Nace, D. A., & Towers, A. L. (2000) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.2000.tb03879.x · Cited by 38
Which Cholinesterase Inhibitor is the Safest for the Heart in Elderly Patients With Alzheimer’s Disease?
Işık, A. T., Bozoğlu, E., Yay, A., et al. (2012) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317512442999 · Cited by 37
“The cholinesterase inhibitors (ChEIs) including donepezil, rivastigmine, and galantamine are currently considered to be the first-line treatment of Alzheimer’s disease (AD).(1) Although the target organ for these drugs is the brain, the heart is also rich in cholinesterases and their inhibition may adversely affect ca…”
Background
Theracurmin Ameliorates Cognitive Dysfunctions in 5XFAD Mice by Improving Synaptic Function and Mitigating Oxidative Stress
Kim, J., Kim, J., Huang, Z., Goo, N., Bae, H. J., Jeong, Y., Park, H. J., Cai, M., Cho, K., Jung, S. Y., et al. (2019) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2019.046 · Cited by 37
“Despite significant improvements in the pharmacotherapy for AD, patients experience several drug-associated adverse effects, such as diarrhea, nausea or insomnia (Shintani and Uchida, 1997; Hashimoto et al., 2000).”
Background
Ethanolic Extract of the Seed of Zizyphus jujuba var. spinosa Ameliorates Cognitive Impairment Induced by Cholinergic Blockade in Mice
Lee, H. E., Lee, S. Y., Kim, J. S., Park, S. J., Kim, J. M., Lee, Y. W., Jung, J. M., Kim, D. H., Shin, B. Y., Jang, D. S., et al. (2013) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2013.043 · Cited by 35
“However, there are several issues to be overcome such as nausea, diarrhea, anorexia, or vomiting (Shintani and Uchida, 1997; Farlow et al., 2011).”
Background
Donepezil
Foster, R. H., & Plosker, G. L. (1999) · PharmacoEconomics · doi:10.2165/00019053-199916010-00009 · Cited by 35
The ethanolic extract of the Eclipta prostrata L. ameliorates the cognitive impairment in mice induced by scopolamine
Jung, W. Y., Kim, H., Park, H. J., Jeon, S. J., Park, H. J., Choi, H. J., Kim, N. J., Jang, D. S., Kim, D. H., & Ryu, J. H. (2016) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2016.06.010 · Cited by 34
“These drugs improve the cognitive functions of AD patients symptomatically, but they produce several adverse effects such as nausea, diarrhea, anorexia, or vomiting (Farlow et al., 2011; Shintani and Uchida, 1997).”
Background
Cerebral ischemia combined with β-amyloid impairs spatial memory in the eight-arm radial maze task in rats
Iwasaki, K., Egashira, N., Hatip‐Al‐Khatib, I., Akiyoshi, Y., Arai, T., Takagaki, Y., Watanabe, T., Mishima, K., & Fujiwara, M. (2006) · Brain Research · doi:10.1016/j.brainres.2006.04.073 · Cited by 34
Pharmacologic treatment of adolescent and child schizophrenia
Young, C., & Findling, R. L. (2004) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.4.1.53 · Cited by 31
Donepezil Derivatives Targeting Amyloid-β Cascade in Alzheimer's Disease
Mezeiová, E., Chalupova, K., Nepovimová, E., Górecki, L., Prchal, L., Maliňák, D., Kuča, K., Soukup, O., & Korábečný, J. (2019) · Current Alzheimer Research · doi:10.2174/1567205016666190228122956 · Cited by 31
Guidelines for the Appropriate Use of Cholinesterase Inhibitors in Patients with Alzheimer??s Disease
Schachter, A. S., & Davis, K. L. (1999) · CNS Drugs · doi:10.2165/00023210-199911040-00004 · Cited by 29
A comparative study of neuroprotective effect of angiotensin converting enzyme inhibitors against scopolamine-induced memory impairments in rats
Kamal, M., Jawaid, T., & Jahan, S. (2015) · Journal of Advanced Pharmaceutical Technology amp Research · doi:10.4103/2231-4040.161514 · Cited by 27
“Donepezil has the advantage of long t1/2, about 70 h.[7] Address for correspondence:”
Background
Cognitive Ameliorating Effect ofAcanthopanax koreanumAgainst Scopolamine-Induced Memory Impairment in Mice
Lee, S. H., Park, H. J., Jeon, S. J., Kim, E., Lee, H. E., Kim, H., Kwon, Y., Zhang, J., Jung, I. H., & Ryu, J. H. (2017) · Phytotherapy Research · doi:10.1002/ptr.5764 · Cited by 27
“Currently, AD therapy has focused on the activation of the cholinergic neurotransmitter system by increasing acetylcholine; thus, donepezil or rivastigmine are widely used clinically as acetylcholinesterase inhibitors (Shintani and Uchida, 1997; Farlow et al., 2011).”
Background
Chaperone-Dependent Mechanisms as a Pharmacological Target for Neuroprotection
Воронин, М. В., Абрамова, Е. В., Verbovaya, E. R., Vakhitova, Y. V., & Середенин, С. Б. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24010823 · Cited by 27
“Donepezil, which has Sigma1R agonist and noncovalent reversible inhibitor of acetylcholinesterase (AChE) properties [360,361], is undergoing phase 3 clinical trials designed to evaluate the drug’s effect on AD symptoms after 6 months of treatment (NCT04661280).”
Background
Structure- and ligand-based drug design of novel p38-alpha MAPK inhibitors in the fight against the Alzheimer’s disease
Pinsetta, F. R., Taft, C. A., & da Silva, C. H. T. D. P. (2013) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2013.803441 · Cited by 25
“Email: catff@terra.com.br Journal of Biomolecular Structure and Dynamics, 2014 Vol. 32, No. 7, 1047–1063, http://dx.doi.org/10.1080/07391102.2013.803441 2013 Taylor & Francis (Mucke, 2009; Pinsetta, Taft, & Silva, 2013; Shintani & Uchida, 1997).”
Influential
Design, synthesis, and structure–activity relationships of 2-benzylidene-1-indanone derivatives as anti-inflammatory agents for treatment of acute lung injury
Xiao, S., Zhang, W., Chen, H., et al. (2018) · Drug Design Development and Therapy · doi:10.2147/dddt.s160314 · Cited by 24
“In addition, several important drugs contain 1-indanone as a core moiety, such as Donepezil, which in 1996 was approved by the US Food and Drug Administration (FDA) for the treatment of moderate-to-severe Alzheimer’s disease.(20) Considering the structural similarity that exists between chalcone and 1-indanone, and si…”
Background
Chironji (Buchanania lanzan) Wonder Tree: Nutritional and Therapeutic Values
Neeraj, R., Bisht, V., & Purwar, S. (2020) · International Journal of Current Microbiology and Applied Sciences · doi:10.20546/ijcmas.2020.902.349 · Cited by 21
3,4-Dihydroquinazoline derivatives inhibit the activities of cholinesterase enzymes
Park, B., Nam, J. H., Kim, J. H., Kim, H. J., Onnis, V., Balboni, G., Lee, K., Park, J. H., Catto, M., Carotti, A., et al. (2017) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2017.01.068 · Cited by 21
Virtual Screening, Molecular Interaction Field, Molecular Dynamics, Docking, Density Functional, and ADMET Properties of Novel AChE Inhibitors in Alzheimer's Disease
da Silva, C. H. T. D. P., Carvalho, I., & Taft, C. A. (2007) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2007.10507140 · Cited by 18
Effect of Colloidal Aqueous Solution of Fullerene (C60) in the Presence of a P-Glycoprotein Inhibitor (Verapamil) on Spatial Memory and Hippocampal Expression of Sirtuin6, SELADIN1, and AQP1 Genes in a Rat Model of Alzheimer’s Disease
Nikpour, M., Sharafi, A., Hamidi, M., & Andalib, S. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00213 · Cited by 16
Role of Pharmacogenomics in Individualizing Treatment for Alzheimer’s Disease
Argueta, N., Notari, E., & Szigeti, K. (2022) · CNS Drugs · doi:10.1007/s40263-022-00915-3 · Cited by 18
“It is primarily metabolized by the hepatic microsomal cytochrome P450 (CYP) system through isoenzymes CYP2D6 and CYP3A4 [12, 13].”
Background
Cardiovascular pharmacodynamics of donepezil hydrochloride on the PR and QT intervals in patients with dementia
Igeta, H., Suzuki, Y., Tajiri, M., et al. (2014) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.2398 · Cited by 17
Effects of Acetylcholinesterase Inhibitors on Balance and Gait Functions and Orthostatic Hypotension in Elderly Patients With Alzheimer Disease
Işık, A. T., Soysal, P., & Usarel, C. (2016) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317516666195 · Cited by 17
“According to this hypothesis, these drugs, which increase acetylcholine concentration, may contribute to the initiation and maintenance of gait by improving attention and executive functions via cerebral cortex; to the control of length of step and walking speed via subcortical cortex (basal ganglia); and to the rhyth…”
Background
A Comparative Study between Lycorine and Galantamine Abilities to Interact with AMYLOID β and Reduce In Vitro Neurotoxicity
Kola, A., Lamponi, S., Currò, F., & Valensin, D. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032500 · Cited by 16
“It was approved for medical use by the FDA in 1996 [24] and is widely used in the USA where it was the 120th most prescribed medication in 2019.”
Method
Management of Alzheimer??s Disease
Ibbotson, T., & Goa, K. L. (2002) · Disease Management & Health Outcomes · doi:10.2165/00115677-200210010-00004 · Cited by 16
Enzyme colorimetric cellulose membrane bioactivity strips based on acetylcholinesterase immobilization for inhibitors preliminary screening
Chen, Y., Zhang, X., & Luo, X. (2023) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2023.113184 · Cited by 15
Cholinergic Treatments of Alzheimer's Disease
Tsopelas, N. D., & Marin, D. B. (2001) · Elsevier eBooks · doi:10.1016/b978-012351830-9/50034-2 · Cited by 15
DONEPEZIL-RELATED TOXIC HEPATITIS
Dierckx, R., & Vandewoude, M. F. J. (2008) · Acta Clinica Belgica · doi:10.1179/acb.2008.066 · Cited by 15
“Single doses of donepezil can be safely administered to patients with moderately to severely impaired renal function (1).”
BackgroundInfluential
Donepezil improves skeletal muscle insulin resistance in obese mice via the AMPK/FGF21-mediated suppression of inflammation and ferroptosis
Gwon, H. J., Cho, W., Choi, S. W., Lim, D. S., Tanrıverdi, E. Ç., El‐Aty, A. M. A., Jeong, J. H., & Jung, T. W. (2024) · Archives of Pharmacal Research · doi:10.1007/s12272-024-01518-w · Cited by 15
“Donepezil, a reversible acetylcholinesterase inhibitor, has traditionally been used in Alzheimer’s disease (AD) therapy to enhance acetylcholine signaling (Shintani and Uchida 1997).”
Impact of CYP2D6, CYP3A5, and ABCB1 Polymorphisms on Plasma Concentrations of Donepezil and Its Metabolite in Patients With Alzheimer Disease
Kagawa, Y., Yamamoto, Y., Ueno, A., et al. (2020) · Therapeutic Drug Monitoring · doi:10.1097/ftd.0000000000000823 · Cited by 13
Hollow urchin-shaped manganese dioxide microspheres immobilized acetylcholinesterase for rapid screening inhibitors from traditional herbal medicines
Liu, J., Ha, W., Zhang, H., & Shi, Y. (2022) · Journal of Chromatography A · doi:10.1016/j.chroma.2022.462824 · Cited by 12
Neurosteroids: Structure-Uptake Relationships and Computational Modeling of Organic Anion Transporting Polypeptides (OATP)1A2
Adla, S. K., Tonduru, A. K., Kronenberger, T., Kudová, E., Poso, A., & Huttunen, K. M. (2021) · Molecules · doi:10.3390/molecules26185662 · Cited by 11
“So far, available drugs (donepezil [1,2] rivastigmine [3,4] galantamine [5,6], and memantine [7,8]) can partially treat only some symptoms of AD.”
Background
Discovery of novel acetylcholinesterase inhibitors through integration of machine learning with genetic algorithm based in silico screening approaches
Khan, M. I., Park, T., Cho, Y., Scotti, L., de Menezes, R. P. B., Husain, F. M., Alomar, S. Y., Baig, M. H., & Dong, J.-J. (2023) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1007389 · Cited by 12
“Donepezil, an AChE inhibitor, is a widely used drug in treating AD and its mechanism of action is very clear (Shintani and Uchida, 1997).”
Background
Alzheimer’s disease
Schachter, A. S., & Davis, K. L. (2000) · Current Treatment Options in Neurology · doi:10.1007/s11940-000-0023-0 · Cited by 13
In silico design of novel pyridazine derivatives as balanced multifunctional agents against Alzheimer’s disease
Aloui, M., fadili, M. E., Mujwar, S., Er-rajy, M., Abuelizz, H. A., Er-Rahmani, S., Zarougui, S., & Elhallaoui, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-98182-x · Cited by 10
An Updated Review on Phyto-Pharmacological and Pharmacognostical Profile Of Buchanania Lanzan : A Pharmacognostic Miracle Herb
Elias, A., Habbu, P. V., & Iliger, S. (2021) · International Journal of Scientific Research in Science and Technology · doi:10.32628/ijsrst218642 · Cited by 9
The Influence of Selected Antipsychotic Drugs on Biochemical Aspects of Alzheimer’s Disease
Podsiedlik, M., Markowicz-Piasecka, M., & Sikora, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094621 · Cited by 11
“[36] allowed us to investigate multiple drug effects on ChEs.”
BackgroundMethod
A Comprehensive Review on Alzheimer’s Disease its Pathogenesis, Epidermiology, Diagnostics and Treatment
Chavan, A. B., Patil, S. R., Patel, A. M., Chaugule, S. V., & Gharal, S. K. (2023) · Journal for Research in Applied Sciences and Biotechnology · doi:10.55544/jrasb.2.4.8 · Cited by 9
“families may not observe a significant immediate amelioration in symptoms; nonetheless, patients undergoing pharmaceutical treatment will exhibit a relatively diminished decline in cognitive function as compared to control groups[24].”
Background
Medetomidine Suppresses Cardiac and Gastric Sympathetic Nerve Activities but Selectively Activates Cardiac Vagus Nerve
Shimizu, S., Akiyama, T., Kawada, T., et al. (2014) · Circulation Journal · doi:10.1253/circj.cj-13-1456 · Cited by 9
Selected phytochemicals as potent acetylcholinesterase inhibitors: An in silico prediction
Shrestha, R. L., Neupane, P., Dhital, S., Parajuli, N., Maharjan, B., Shrestha, T., Bharati, S., Marasini, B. P., & Subin, J. A. (2024) · Journal of the Serbian Chemical Society · doi:10.2298/jsc240405065s · Cited by 8
Rivastigmine improves dual-task gait velocity in patients with Alzheimer’s disease
Shimura, H., Aiba, S., Hayashi, A., et al. (2021) · BMC Neurology · doi:10.1186/s12883-021-02098-8 · Cited by 8
Protective Effects of Compounds from Cimicifuga dahurica against Amyloid Beta Production in Vitro and Scopolamine-Induced Memory Impairment in Vivo
Lee, S.-B., Yang, S. Y., Thảo, N. P., et al. (2020) · Journal of Natural Products · doi:10.1021/acs.jnatprod.9b00543 · Cited by 7
Synthesis and Molecular Modeling Studies of 1-Benzyl-2-Indolinones As Selective AChE Inhibitors
Apaydın, Ç. B., Eter, Ö. S., Eraslan‐Elma, P., Özsoy, N., & Karalı, N. (2022) · Future Medicinal Chemistry · doi:10.4155/fmc-2022-0139 · Cited by 7
Pyrazoline-based Mycobactin analogues as dual inhibitors of MAO/Cholinesterase
Jayaprakash, V., Yabanoğlu, S., Ucar, B. I., et al. (2011) · doi:10.13140/rg.2.1.1920.3921 · Cited by 6
Bioequivalence study of Donepezil hydrochloride in healthy Korean volunteers
Choi, Y., Rhee, S., Jang, I., et al. (2015) · Translational and Clinical Pharmacology · doi:10.12793/tcp.2015.23.1.26 · Cited by 5
“[1] The daily-recommended dose of donepezil is 5 to 10 mg.[2] The dose can be increased depending on the patient’s clinical condition.”
Background
Design, synthesis, structure, toxicology and in vitro testing of three novel agents for Alzheimer’s disease
Figueroa‐Villar, J. D. (2017) · RSC Advances · doi:10.1039/c6ra27042e · Cited by 5
Investigation of Anticancer Properties of 2-benzylidene-1-indanone and Its Derivatives by DFT and Molecular Docking
Yıldız, C. A., & Erkan, S. (2024) · Turkish computational and theoretical chemistry/Turkish computational and theoretical chemistry : · doi:10.33435/tcandtc.1399916 · Cited by 5
An insight into the morphological, ethno medicinal, phytochemical and pharmaceutical properties of Buchanania lanzan
Mondal, M., Konar, A., Halder, S., et al. (2024) · Journal of Medicinal Plants Studies · doi:10.22271/plants.2024.v12.i1a.1620 · Cited by 4
Synthesis and Molecular Docking Studies of 5-Trifluoromethoxy-2-Indolinones as Cholinesterase Dual Inhibitors
Eter, Ö. S., Özsoy, N., & Karalı, N. (2024) · Future Medicinal Chemistry · doi:10.4155/fmc-2023-0281 · Cited by 5
Ethanolic Extract of Opuntia ficus-indica var. saboten Ameliorates Cognitive Dysfunction Induced by Cholinergic Blockade in Mice
Kwon, Y., Liao, Y., Koo, B., Bae, H., Zhang, J., Han, E. H., Yun, S. M., Lim, M. K., Lee, S. H., Jung, S. Y., et al. (2018) · Journal of Medicinal Food · doi:10.1089/jmf.2017.4131 · Cited by 4
“5 These drugs exhibit therapeutic potential in patients with moderate AD, but some adverse effects were reported, such as nausea, vomiting, or diarrhea.”
Diarrhea in Old Age
Ratnaike, R. N. (2003) · KARGER eBooks · doi:10.1159/000072622 · Cited by 4
Alzheimer′s disease, anesthesia and the cholinergic system
Kapoor, M. (2011) · Journal of Anaesthesiology Clinical Pharmacology · doi:10.4103/0970-9185.81817 · Cited by 4
“Peripheral cholinergic adverse effects of ChIs include nausea, vomiting, diarrhea, dizziness, syncope and even seizure and they may cause discontinuation of therapy.[20,21] Seizures can also be due to the disease process itself.”
Background
Two new iridoids and triterpenoid analogues from the leaves of Viburnum chingii and their anti-acetylcholinesterase activity
Liang, J., Lv, T., Xu, Z., et al. (2022) · Fitoterapia · doi:10.1016/j.fitote.2022.105400 · Cited by 3
Estudos de modelagem molecular e relação estrutura-atividade da acetilcolinesterase e inibidores em Mal de Alzheimer
de Almeida, J. R. (2011) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.60.2011.tde-21032011-102116 · Cited by 3
Donepezil-derived multi-target-directed ligands: design, synthesis, and anti-Alzheimer's evaluation
Bassiouny, M. S., Shahin, M. I., Jaballah, M. Y., Ahmed, T. E., Henary, M., & Samir, N. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.109924 · Cited by 3
Alzheimer's Disease, Acetylcholine and Oestrogen
Perry, E. (1998) · The Journal of the British Menopause Society · doi:10.1177/136218079800400406 · Cited by 2
Quinase p38 alfa como alvo para o planejamento de fármacos em Mal de Alzheimer
Pinsetta, F. R. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.60.2013.tde-06092013-104102 · Cited by 1
Recovery of function after lesions of the anterior thalamic nuclei: CA1 neuromorphology
Harland, B. C. (2013) · doi:10.26021/5935 · Cited by 1
Donepezil for the management of patients with Alzheimer's disease: a good choice from among the cholinesterase inhibitors
&NA; (2001) · Drugs & Therapy Perspectives · doi:10.2165/00042310-200117110-00001 · Cited by 1
The Role of Hypertensive Vascular Disease in Brain Aging and Neurodegeneration
Raji, C. A. (2009) · D-Scholarship@Pitt (University of Pittsburgh)
Planejamento racional de inibidores da beta-secretase em mal de Alzheimer
Semighini, E. P. (2013) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.60.2013.tde-06092013-102421
Understanding the medical treatment of dementia
Nazarko, L. (2006) · Nursing and Residential Care · doi:10.12968/nrec.2006.8.2.20352
Isquemia miocárdica en una paciente en tratamiento con donepezilo
Egido, A., Sena, F., Lechuga, Í., et al. (2000) · Medicina Clínica · doi:10.1016/s0025-7753(00)71384-4
Donepezilof its Use in Alzheimer's Disease
Erzigkeit, H., Hayashi, K., Jhee, S. S., et al. (2000)
Nutritional strategies in the management of Alzheimer\'s disease: systematic review and meta-analysis
Fernández, S. S. M. (2016) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.89.2016.tde-19102016-165329
Donepezil Implications of Therapy
Bayer, A. J., Brodaty, H., Dalziel, W. B., et al. (1999)
Donepezil
Clarke, Z. (2007) · xPharm: The Comprehensive Pharmacology Reference · doi:10.1016/b978-008055232-3.61642-3

Authors: Shintani, E. Y., & Uchida, K. M.
Affiliations: MemorialCare Long Beach Medical Center (US)
University of California, Irvine Medical Center (US)
Corresponding author: Shintani, Ellen Y.
Venue: American Journal of Health-System Pharmacy
Publisher: Oxford University Press (OUP)
Published: 1997-12-15
Volume: 54
Issue: 24
Pages: 2805-2810
ISSN: 1079-2082 (ISSN-L)
1535-2900
DOI: 10.1093/ajhp/54.24.2805
OpenAlex: W1820407896
Cited by: 108
References: 0
Citations by year: 2026: 4 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 3 · 2013: 6 · 2012: 3
FWCI: 4.17
Type: journal article
Language: en
Open access: closed
Locations: American Journal of Health-System Pharmacy (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: donepezil, acetylcholinesterase inhibitors, Alzheimer's disease, dementia, tacrine, pharmacokinetics, adverse drug reactions, drug interactions, dosage and administration, hepatotoxicity, cognitive function
MeSH terms: Donepezil, Aged, Alzheimer Disease, Anorexia, Cholinesterase Inhibitors, Diarrhea, Drug Administration Schedule, Drug Interactions, Humans, Indans, Nausea, Piperidines

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Donepezil: an anticholinesterase inhibitor for Alzheimer’s disease

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cited by

Related

Metadata

Record

About these checks