A retrospective review of memantine use and COVID‐19‐associated mortality from a national database

Park, Moon Ho; Kwon, Do Young

doi:10.1002/jmv.26266

Cited by 6 publications

(4 citation statements)

References 4 publications

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“…following documented exposure but none of them went on to develop clinical manifestations of infectious disease [43]. Similar findings were subsequently independently reported in a patient with type-2 diabetes and members of his immediate family all of whom tested positive for COVID-19 and were being treated with amantadine as well as in a further case of an amantadine-treated patient with Parkinson's disease [44,45]. In a related study, treatment with memantine [10 mg bid] was reported to manifest apparently protective effects in a group of 7 patients with cognitive impairment who tested positive for COVID-19 [42].…”

Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalsupporting

confidence: 69%

“…A retrospective study of a national database of 5726 patients, 140 of whom subsequently died, did not reveal any statistical difference in mortality of a group of patients between COVID-19 associated mortality and ongoing treatment with memantine for dementia, indicating it's not likely to have therapeutic effects on patients with COVID-19, however it did not seem to have any deleterious effects [45].…”

Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalmentioning

confidence: 96%

“…Consequently, much reliance and activity is devoted for the moment on the reports of individual cases that are, by necessity, generally uncontrolled and observational in nature. However, results of three published reports have appeared so far involving a total of 24 patients in which there is subjective evidence of a protective effect of amantadine or memantine against COVID-19 including patients with comorbidities or severe neurological disorders [42][43][44][45]. following documented exposure but none of them went on to develop clinical manifestations of infectious disease [43].…”

Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalmentioning

confidence: 99%

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Repurposing of Adamantanes with Transmitter Receptor Antagonist Properties for the Prevention/Treatment of COVID-19

Brenner¹

2020

J Pharm Pharmacol

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Members of the adamantane family of agents in general and two such members, amantadine and memantine, in particular, have established beneficial actions across a wide range of infectious diseases including those caused by coronaviruses. Increasing evidence suggests that the protective effects of these agents is the result of actions on neurotransmitter systems namely the NMDA receptor subclass of the glutamatergic system and by the α7-nACh subclass of nicotinic cholinergic receptor. The potent NMDA receptor antagonist, memantine, prevents motor disabilities and reduces replication of the neuroinvasive/neurotropic human respiratory virus HCoV-OC43 dose-dependently. Moreover, the lysosomotrophic adamantanes amantadine and memantine also limit viral replication. Known lysomotrophic agents such as ammonium chloride inhibit cellular entry of SARS-CoV-2 on laboratory testing. Inhibiting clathrinmediated endocytosis (cellular entry) of the SARS-CoV-2/ACE2 complex by amantadine or rimantadine may block viral entry into vulnerable cellular populations, and also reduce platelet activating factor-priming of Polymorphonuclear [PMN] cells, potentially lessening PMN cell-mediated tissue damage and excess Neutrophil Extracellular Traps [NETs] seen in advanced cases of COVID-19. Rimantadine has inhibitory effects of SARS-CoV-1, a closely-related virus to SARS-CoV-2, which may indicate the need for further evaluation as a treatment for COVID-19. Amantadine increases Dopamine [DA] release and blocks its reuptake, increasing its action on DA receptors on T cells thus activating resting effector T cells and suppressing regulator T cells, which may have a beneficial immunomodulating function in infectious diseases. Proposed adverse effects of smoking on COVID-19 outcomes are attributed to the effects of nicotine via the α7-nACh receptor located on bronchial and alveolar epithelial cells. As an antagonist of this receptor, memantine has the potential to prevent the entry of SARS-CoV-2 into these cells. Independent case reports provide evidence of protective effects of amantadine and/or memantine against COVID-19. Additional epidemiologic studies however indicate a lower incidence of smoking in hospitalized patients, stimulating investigations of nicotine-related aspects, and amino acid sequence analysis indicate homologous sequences with those of neurotoxins seen in snake venoms blocking the α7-nAChR suggesting that COVID-19 may be a disease of the nicotinic cholinergic system; α7-nAChR is involved in the cholinergic anti-inflammatory pathway or reflex. COVID-19 is a biphasic disease, the initial aspect involved with the initial infection and viral replication which stimulates a prominent innate immune response. This then transitions to the adaptive immune response with suppression of infection and recovery, while the innate response is suppressed via the cholinergic anti-inflammatory pathway. Severe disease may occur when the initial innate immune response continues, the cholinergic anti-inflammatory pathway being arrested by the neu...

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Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalsupporting

confidence: 69%

Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalmentioning

confidence: 96%

Section: Memantine or Amantadine For Prevention Of Covid-19: Clinicalmentioning

confidence: 99%

See 1 more Smart Citation

Repurposing of Adamantanes with Transmitter Receptor Antagonist Properties for the Prevention/Treatment of COVID-19

Brenner¹

2020

J Pharm Pharmacol

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“…A few case reports suggest a possible beneficial effect of amantadine on the clinical course of COVID-19 53 . An observational study using a national Korean database found no effect of memantine on the course of COVID-19 disease 54 . Further clinical data for either drug in COVID-19 patients is not available.…”

Section: Other Neuropsychiatric Drugsmentioning

confidence: 98%

Neuropsychiatric Drugs Against COVID-19: What is the Clinical Evidence?

2022

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Since the beginning of the coronavirus disease (COVID)-19 pandemic, the need for effective treatments for COVID-19 led to the idea of “repurposing” drugs for antiviral treatment. Several antipsychotics and antidepressants have been tested for in vitro activity against the severe acute respiratory syndrome coronavirus 2. Chlorpromazine, other phenothiazine antipsychotics, and the antidepressant fluoxetine were found to be rather potent in these studies. However, whether effective plasma concentrations can be obtained with clinically accepted doses of these drugs is not clear. Data of COVID-19 patients are not yet available but several clinical studies are currently underway.The specific serotonin reuptake inhibitor fluvoxamine is a potent Sigma-1 receptor agonist and reduces inflammation in animal models of cytokine-stress. Accordingly, fluvoxamine treatment was superior to placebo in reducing impaired respiratory function and other symptoms of inflammation in COVID-19 patients in a placebo-controlled clinical study and another open clinical trial. The beneficial effects of fluvoxamine on the course of COVID-19 were recently confirmed in a large placebo-controlled double-blind trial with several hundred patients.Inflammation represents a major risk factor for many psychiatric disorders which explains the high susceptibilitiy of COVID-19 patients for psychiatric diseases. Many antidepressants and antipsychotics possess anti-inflammatory properties independent of sigma-1 activity which might be important to reduce psychiatric symptoms of COVID-19 patients and to improve respiratory dysfunction and other consequences of inflammation. This might explain the rather unspecific benefit which has been reported for several cohorts of COVID-19 patients treated with different psychotropic drugs.

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