Repurposing Donepezil to Treat COVID-19: A Call for Retrospective Analysis of Existing Patient Datasets

Murali, Meena M; Phillips, J. C.

doi:10.46889/jcim.2021.2305

Cited by 2 publications

(8 citation statements)

References 105 publications

(129 reference statements)

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“…Drug Administration (FDA) to treat various stages of AD, and most studies have examined the effect of this drug on AD (5,10), donepezil has some therapeutic potential in other dementia and non-dementia diseases such as improving movement and dementia in Parkinson's disease and positively affecting sleep disorders, psychiatric diseases, and even infectious diseases (11)(12)(13)(14). Therefore, we aimed to review these effects in the present study, in addition to the role of this drug in treating AD.…”

Section: Contextmentioning

confidence: 99%

“…According to studies, in addition to therapeutic applications in neurological and psychiatric diseases, donepezil can have different effects on the immune system through different mechanisms. Donepezil can affect innate and acquired immune systems through different pathways (14,92,93).…”

Section: Immune System and Infectious Diseasementioning

confidence: 99%

“…Acetylcholine reduces the production of inflammatory cytokines via modulating nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) gene expression in macrophage cells, which play a fundamental role in the immune system's response to pathogens and inflammatory processes by binding to the alpha-7 nicotinic receptors on these cells. Acetylcholine also modulates the immune system and reduces neutrophil leakage by binding to muscarinic receptors in many cell populations (Figure 1) (14,92,(94)(95)(96).…”

Section: Immune System and Infectious Diseasementioning

confidence: 99%

“…According to studies, the cholinergic system seems to play an influential role in modulating lung inflammation, especially in infections, and maintaining normal lung function. Increased secretion of acetylcholine following lung inflammation can help modulate inflammation and repair damaged lung tissue by various pathways, such as shifting the macrophages population to M2 macrophages, which secrete anti-inflammatory cytokines and play an anti-inflammatory role in inflammatory processes, regulating the differentiation and growth of airway cells to improve the function of the epithelium of these ducts, which are altered by inflammatory cytokines, reducing neutrophil leakage from these ducts, and increasing cholinergic lymphocytes in the lungs, which play an influential role in regulating inflammatory processes (Figure 1) (14). A retrospective study by Abe et al also showed this effect.…”

Section: Immune System and Infectious Diseasementioning

confidence: 99%

“…The studies showed that fatal acute respiratory distress syndrome (ARDS), sepsis, cytokine storm, cardiovascular damage, disseminated intravascular coagulation (DIC), and acute kidney damage could be inhibited via this drug. These effects seem to be due to the immunomodulatory effects of donepezil on innate and acquired immune systems (14).…”

Section: Immune System and Infectious Diseasementioning

confidence: 99%

See 4 more Smart Citations

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

et al. 2022

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: Donepezil hydrochloride is an acetylcholine esterase inhibitor studied and approved to treat Alzheimer's disease (AD). However, this drug can have positive therapeutic potential in treating different conditions, including various neurodegenerative disorders such as other types of dementia, multiple sclerosis, Parkinson's disease, psychiatric and mood disorders, and even infectious diseases. Hence, this study reviewed the therapeutic potential of this drug in treating Alzheimer's and other diseases by reviewing the articles from databases including Web of Science, Scopus, PubMed, Cochrane, and Science Direct. It was shown that donepezil could affect the pathophysiology of these diseases via mechanisms such as increasing the concentration of acetylcholine, modulating local and systemic inflammatory processes, affecting acetylcholine receptors like nicotinic and muscarinic receptors, and activating various cellular signaling via receptors like sigma-1 receptors. Despite many therapeutic potentials, this drug has not yet been approved for treating non-Alzheimer's diseases, and more comprehensive studies are needed.

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Section: Contextmentioning

confidence: 99%

Section: Immune System and Infectious Diseasementioning

confidence: 99%

Section: Immune System and Infectious Diseasementioning

confidence: 99%

Section: Immune System and Infectious Diseasementioning

confidence: 99%

Section: Immune System and Infectious Diseasementioning

confidence: 99%

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Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

et al. 2022

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Donepezil-associated survival benefits among Alzheimer’s disease patients are retained but not enhanced during COVID-19 infections

Edmiston

Bej

Wilson

et al. 2023

Therapeutic Advances in Infection

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Background and Aim: Donepezil is a front-line treatment for Alzheimer’s disease. Donepezil treatment is associated with decreased risk of all-cause mortality. Specific protection is observed in pneumonia and cardiovascular disease. We hypothesized that donepezil treatment would improve mortality among Alzheimer’s patients following infection with COVID-19. The objective of this study is to assess the influence of ongoing donepezil treatment on survival in Alzheimer’s disease patients after polymerase chain reaction (PCR)-confirmed COVID-19 infection. Methods: This is a retrospective cohort study. We conducted a national survey of Veterans with Alzheimer’s disease to assess the influence of ongoing donepezil treatment on survival in Alzheimer’s disease patients after PCR-confirmed COVID-19 infection. We assessed all-cause 30-day mortality stratified by COVID-19 infection and donepezil use, estimating odds ratios using multivariate logistic regression. Results: Among people with Alzheimer’s disease and COVID-19, all-cause 30-day mortality was 29% (47/163) for people taking donepezil compared with 38% (159/419) for those who were not. Among people with Alzheimer’s disease without COVID-19, all-cause 30-day mortality was 5% (189/4189) for people taking donepezil compared with 7% (712/10,241) for those who were not. Adjusting for covariates, the decrease in mortality associated with donepezil did not differ between people with and without COVID-19 (interaction p = 0.710) Conclusion: The known survival benefits of donepezil were retained but not found to be specific to COVID-19 among people with Alzheimer’s disease.

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Repurposing Donepezil to Treat COVID-19: A Call for Retrospective Analysis of Existing Patient Datasets

Cited by 2 publications

References 105 publications

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil Beyond Alzheimer's Disease? A Narrative Review of Therapeutic Potentials of Donepezil in Different Diseases

Donepezil-associated survival benefits among Alzheimer’s disease patients are retained but not enhanced during COVID-19 infections

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