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Donepezil

InterventionApproved 1996

5 papers10 findings

PubChem 3152ChEBI 145499MeSH D000077265

C, W, M, H: cells, worms or flies, mice, humans. Dark: independent labs found the same change there. Light: one lab or one study. Outline: nothing yet.

Labs are independent when their papers share no last author and no institution.

Against: findings that point the other way from most findings on the same outcome.

On aging: the drug’s trials ARN judged to be about aging, of every trial that tests it for any use.

No results posted: trials that ended more than a year ago with no results on ClinicalTrials.gov and no paper in ARN’s record.

Company ties: findings with an author at a company, or from a paper whose competing-interests statement declares ties to one.

  • 3 independent labs in 2 countries
  • 0 on aging of 153 trials, 69 with no results posted
  • Funders: San Diego State University and others
  • 41 of 153 trials sponsored by its developers
  • Human trial1
  • Animals4

Outcomes

10

Bronchus-associated lymphoid tissue

upin mice1

1 study

  1. Donepezil increases bronchus-associated lymphoid tissue in mice.

    “Donepezil treatment also dramatically increased bronchus-associated lymphoid tissue (iBALT) formation.”

    Animalslungsix months

    Acetylcholinesterase Inhibition Reverses Age-Related Pulmonary Decline and Increases Bronchus-Associated Lymphoid Tissue Formation in Aged Mice

    Biology3 Feb 2026

More on Bronchus-associated lymphoid tissue

Elastic fibers

upin mice1

1 study

  1. Donepezil increases elastic fibers in mice.

    “treated mice showed a reversal of alveolar enlargement (a hallmark of emphysema) and complete restoration of elastic fibers.”

    Animalslungsix months

    Acetylcholinesterase Inhibition Reverses Age-Related Pulmonary Decline and Increases Bronchus-Associated Lymphoid Tissue Formation in Aged Mice

    Biology3 Feb 2026

More on Elastic fibers

Alveolar enlargement

downin mice1

1 study

  1. Donepezil decreases alveolar enlargement in mice.

    “treated mice showed a reversal of alveolar enlargement (a hallmark of emphysema) and complete restoration of elastic fibers.”

    Animalslungsix months

    Acetylcholinesterase Inhibition Reverses Age-Related Pulmonary Decline and Increases Bronchus-Associated Lymphoid Tissue Formation in Aged Mice

    Biology3 Feb 2026

Voluntary activity

upin mice1

1 study

  1. Donepezil improves voluntary activity in mice.

    “After six months, blood oxygen saturation and voluntary activity were significantly improved.”

    Animalssix months

    Acetylcholinesterase Inhibition Reverses Age-Related Pulmonary Decline and Increases Bronchus-Associated Lymphoid Tissue Formation in Aged Mice

    Biology3 Feb 2026

Blood oxygen saturation

upin mice1

1 study

  1. Donepezil improves blood oxygen saturation in mice.

    “After six months, blood oxygen saturation and voluntary activity were significantly improved.”

    Animalsbloodsix months

    Acetylcholinesterase Inhibition Reverses Age-Related Pulmonary Decline and Increases Bronchus-Associated Lymphoid Tissue Formation in Aged Mice

    Biology3 Feb 2026

More on Blood oxygen saturation

Beam slips

downin mice1

1 study

  1. Donepezil decreases beam slips in mice.

    “DON increased midpoint screen hang time and reduced endpoint beam slips in the Cisd2KO.”

    Animalsin Cisd2KO mice11-wk

    Donepezil treatment, alone or combined with exercise, enhances skeletal muscle function in healthy and advanced aging disease mouse models

    Journal of applied physiology (Bethesda, Md. : 1985)14 Nov 2025

Oxidative phosphorylation

upin mice1

1 study

  1. Donepezil improves oxidative phosphorylation in mice.

    “Furthermore, DON increased nonresting energy expenditure and improved palmitate-dependent mitochondrial respiration in the gastrocnemius muscle in WT”

    Animalsin WT micegastrocnemius11-wk

    Donepezil treatment, alone or combined with exercise, enhances skeletal muscle function in healthy and advanced aging disease mouse models

    Journal of applied physiology (Bethesda, Md. : 1985)14 Nov 2025

More on Oxidative phosphorylation

Screen hanging time

upin mice1

1 study

  1. Donepezil improves screen hanging time in mice.

    “In WT mice, DON improved screen hanging time at the midpoint and increased grip strength at the endpoint of the 11-wk study.”

    Animalsskeletal muscle11-wk

    Donepezil treatment, alone or combined with exercise, enhances skeletal muscle function in healthy and advanced aging disease mouse models

    Journal of applied physiology (Bethesda, Md. : 1985)14 Nov 2025

Grip strength

upin mice1

1 study

  1. Donepezil increases grip strength in mice.

    “In WT mice, DON improved screen hanging time at the midpoint and increased grip strength at the endpoint of the 11-wk study.”

    Animalsskeletal muscle11-wk

    Donepezil treatment, alone or combined with exercise, enhances skeletal muscle function in healthy and advanced aging disease mouse models

    Journal of applied physiology (Bethesda, Md. : 1985)14 Nov 2025

Reaction time

upin rats1

1 study

  1. Donepezil improves reaction time in rats.

    “Donepezil improved the performance of aged rats by accelerating their responses at a dose of 0.03 mg/kg.”

    Animalsaged rats0.03 mg/kg

    Differential cognitive enhancer effects of acetylcholinesterase inhibitors and memantine on age-related deficits in vigilance and sustained attention: a preclinical validation study

    Behavioral and brain functions : BBF28 Oct 2025

Trials

0 on aging of 153

Approved

Repurposing

All 31

In trials

  • Cognition Disorders

    Phase 4Results posted5 trials

  • Memory Disorders

    Phase 4Completed4 trials

  • Sleep Apnea Syndromes

    Phase 4Results posted3 trials

  • Anosmia

    Phase 4Results posted2 trials

  • Neuralgia

    Phase 4Terminated2 trials

  • Sleep Deprivation

    Phase 4Completed2 trials

All 19

  • Radiation Injuries

    Phase 3Results posted5 trials

  • Astrocytoma

    Phase 3Results posted3 trials

  • Brain Neoplasms

    Phase 3Results posted3 trials

  • Choroid Plexus Neoplasms

    Phase 3Results posted3 trials

  • Dementia of Alzheimer Type

    Phase 3Status unknown2 trials

  • Glioma

    Phase 3Results posted2 trials

  • Meningioma

    Phase 3Results posted2 trials

  • Oligodendroglioma

    Phase 3Results posted2 trials

  • Small cell lung carcinoma

    Phase 3Completed1 trial

  • Autistic Disorder

    Phase 2Results posted3 trials

  • Central Nervous System Neoplasms

    Phase 2Completed3 trials

  • Medulloblastoma

    Phase 2Completed2 trials

  • Sleep Wake Disorders

    Phase 2Results posted2 trials

Stopped

  • NCT00165750TerminatedAlzheimer's disease

    Lack of patients to enroll.

  • NCT01743976TerminatedNeuralgia

    Failure to recruit subjects

  • NCT02487082TerminatedAutism spectrum disorder

    too few subjects enrolled

  • NCT00675025TerminatedDown syndrome

    Sufficient evidence of efficacy not met. Discontinuation not based on any safety concerns.

  • NCT01633593Terminated

    Difficulty in recruiting subjects for the trial.

Trial sponsors

Latest

Nov 2025: 1Dec 2025: 1Jan 2026: 0Feb 2026: 1Mar 2026: 0Apr 2026: 0May 2026: 0Jun 2026: 0Jul 2026: 0Aug 2026: 0Sep 2026: 0Oct 2026: 25 in 12 months
Journal of Neurology

Multimodal PET and MRI predict dementia with Lewy bodies

Combined occipito-parietal cortex pathology and striatal dopamine loss predicted conversion to dementia with Lewy bodies with a sub-distribution hazard ratio of 38.68.Combined occipito-parietal cortex pathology and striatal dopamine loss predicted conversion to dementia with Lewy bodies with a sub-distribution hazard ratio of 38.68.

Cohort study of 21 peopleDementia with Lewy bodies
Paper

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