Effect of Disulfiram on Cognition, Subjective Response, and Cortical‐Event‐Related Potentials in Nonalcoholic Subjects

Sc, Peeke; Ar, Prael; Ri, H. dal; Rogers, Walter K.; Nl, Benowitz; Rt, Jones

doi:10.1111/j.1530-0277.1979.tb05304.x

Cited by 19 publications

(6 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using a more typical dosage of 0.5 g/day, Peeke and colleagues reported in non-alcoholic volunteers over two weeks on a psycholocigal test battery very few significant differences between baseline and disulfiram-treated sessions. Interestingly, these were in the opposite direction to that expected and demonstrated improvement under disulfiram-medication (DSS task, confusion assessment 46 ). Predicting a beneficial outcome for Alzheimer patients under therapy with disulfiram thus remains difficult, even in the light of the encouraging data from the mouse model.…”

Section: Discussionmentioning

confidence: 72%

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Reinhardt

Stoye

Luderer

et al. 2018

Sci Rep

View full text Add to dashboard Cite

ADAM10 is a metalloproteinase acting on the amyloid precursor protein (APP) as an alpha-secretase in neurons. Its enzymatic activity results in secretion of a neuroprotective APP cleavage product (sAPP-alpha) and prevents formation of the amyloidogenic A-beta peptides, major hallmarks of Alzheimer’s disease (AD). Elevated ADAM10 levels appeared to contribute to attenuation of A-beta-plaque formation and learning and memory deficits in AD mouse models. Therefore, it has been assumed that ADAM10 might represent a valuable target in AD therapy. Here we screened a FDA-approved drug library and identified disulfiram as a novel ADAM10 gene expression enhancer. Disulfiram increased ADAM10 production as well as sAPP-alpha in SH-SY5Y human neuronal cells and additionally prevented A-beta aggregation in an in vitro assay in a dose-dependent fashion. In addition, acute disulfiram treatment of Alzheimer model mice induced ADAM10 expression in peripheral blood cells, reduced plaque-burden in the dentate gyrus and ameliorated behavioral deficits. Alcohol-dependent patients are subjected to disulfiram-treatment to discourage alcohol-consumption. In such patients, enhancement of ADAM10 by disulfiram-treatment was demonstrated in peripheral blood cells. Our data suggest that disulfiram could be repurposed as an ADAM10 enhancer and AD therapeutic. However, efficacy and safety has to be analyzed in Alzheimer patients in the future.

show abstract

Section: Discussionmentioning

confidence: 72%

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Reinhardt

Stoye

Luderer

et al. 2018

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Furthermore, pharmacological agents commonly used in withdrawal treatment, e.g. benzodiazepines, may reduce ERP amplitudes [Meador, 1995], whereas disulfiram may increase them [Peeke et al, 1979].…”

Section: Effects Of Chronic Drinking and Withdrawal In Abstinent Alcomentioning

confidence: 99%

Acute and Chronic Effects of Alcohol on Preattentive Auditory Processing as Reflected by Mismatch Negativity

et al. 2000

View full text Add to dashboard Cite

Chronic alcoholism, a major worldwide health problem, is associated with a variety of neurocognitive changes in the afflicted individuals. The precise neurophysiological basis of these changes is not yet understood. Mismatch negativity (MMN) is a preattentive event-related potential component indexing cortical auditory memory traces and automatic change detection in the brain that can be used to study the neural basis of cognitive impairments in various neurodegenerative diseases. MMN studies have revealed that even a low dose of acute alcohol significantly impairs automatic change detection and involuntary attention shifting. Recent MMN results on chronic alcoholism in turn suggest that auditory sensory traces decay slightly faster and are substantially more vulnerable to the distracting effect of backward masking in alcoholics than in healthy subjects. Furthermore, chronic alcohol abuse might accelerate the age-related impairment of automatic change detection. There is also evidence that the MMN changes might predict impaired performance in behavioral memory and attention tasks in alcoholics. In MMN studies of detoxified alcoholics, however, many confounding factors have to be taken into account. For instance, postwithdrawal brain hyperexcitability might be associated with a slightly enhanced or accelerated MMN/MMNm (the magnetic equivalent of MMN). In sum, MMN and MMNm provide an objective noninvasive tool for exploring the neurophysiological functional deficits related to both acute alcohol intoxication and chronic alcoholism.

show abstract

“…Disulfiram has been widely used to treat alcoholism for over 60 years without severe side effects [79]. Cognitive effects of disulfiram in non-alcohol-dependent individuals have been evaluated in one study showing no effect on cognition after two weeks of disulfiram treatment [80]. However, no studies on cognitive effects of long term disulfiram treatment exist [81].…”

Section: Discussionmentioning

confidence: 99%

Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia

Koch

Kauppi

Chen

2022

Preprint

View full text Add to dashboard Cite

In the protein-protein interactome, we have previously identified a significant overlap between schizophrenia risk genes and genes associated with cognitive performance. Here, we further studied this overlap to identify potential candidate drugs for repurposing to treat the cognitive symptoms in schizophrenia. We first defined a cognition-related schizophrenia interactome from network propagation analyses, and identified drugs known to target more than one protein within this network. Thereafter, we used gene expression data to further select drugs that could counteract schizophrenia-associated gene expression perturbations. Additionally, we stratified these analyses by sex to identify sex-specific pharmacological treatment options for the cognitive symptoms in schizophrenia. After excluding drugs contraindicated in schizophrenia, we identified eight drug candidates, most of which have anti-inflammatory and neuroprotective effects. Due to gene expression differences in male and female patients, four of those drugs were also selected in our male-specific analyses, and the other four in the female-specific analyses. Based on our bioinformatics analyses of disease genetics, we suggest eight candidate drugs that warrant further examination for repurposing to treat the cognitive symptoms in schizophrenia, and suggest that these symptoms could be addressed by sex-specific pharmacological treatment options.

show abstract

Effect of Disulfiram on Cognition, Subjective Response, and Cortical‐Event‐Related Potentials in Nonalcoholic Subjects

Abstract: The effect of 0.5 g of disulfiram per day for 2 wk on a battery of cognitive and cortical-event-related potential tasks was studied in healthy, nonalcoholic volunteers.

Cited by 19 publications

References 8 publications

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks

Acute and Chronic Effects of Alcohol on Preattentive Auditory Processing as Reflected by Mismatch Negativity

Candidates for Drug Repurposing to Address the Cognitive Symptoms in Schizophrenia

Contact Info

Product

Resources

About