Disulfiram: Mechanisms, Applications, and Challenges

Background: Since disulfiram’s discovery in the 1940s and its FDA approval for alcohol use disorder, other indications have been investigated. This review describes potential clinical applications, associated risks, and challenges. Methods: For this narrative review, a PubMed search was conducted for articles addressing in vivo studies of disulfiram with an emphasis on drug repurposing for the treatment of human diseases. The key search terms were “disulfiram” and “Antabuse”. Animal studies and in vitro studies highlighting important mechanisms and safety issues were also included. Results: In total, 196 sources addressing our research focus spanning 1948–2022 were selected for inclusion. In addition to alcohol use disorder, emerging data support a potential role for disulfiram in the treatment of other addictions (e.g., cocaine), infections (e.g., bacteria such as Staphylococcus aureus and Borrelia burgdorferi, viruses, parasites), inflammatory conditions, neurological diseases, and cancers. The side effects range from minor to life-threatening, with lower doses conveying less risk. Caution in human use is needed due to the considerable inter-subject variability in disulfiram pharmacokinetics. Conclusions: While disulfiram has promise as a “repurposed” agent in human disease, its risk profile is of concern. Animal studies and well-controlled clinical trials are needed to assess its safety and efficacy for non-alcohol-related indications.

[1]  F. Fernández-Campos,et al.  The Efficacy and Biopharmaceutical Properties of a Fixed-Dose Combination of Disulfiram and Benzyl Benzoate , 2022, International journal of molecular sciences.

[2]  M. Schlitzer,et al.  Disulfiram and dithiocarbamate analogues demonstrate promising antischistosomal effects. , 2022, European journal of medicinal chemistry.

[3]  R. Saraiva,et al.  The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance , 2022, Frontiers in Cellular and Infection Microbiology.

[4]  M. Vedadi,et al.  Kinetic Characterization of SARS-CoV-2 nsp13 ATPase Activity and Discovery of Small-Molecule Inhibitors , 2022, ACS infectious diseases.

[5]  M. Chovanec,et al.  Phase II study of Disulfiram and Cisplatin in Refractory Germ Cell Tumors. The GCT-SK-006 phase II trial , 2022, Investigational New Drugs.

[6]  Y. Li,et al.  Drug D, a Diosgenin Derive, Inhibits L-Arginine-Induced Acute Pancreatitis through Meditating GSDMD in the Endoplasmic Reticulum via the TXNIP/HIF-1α Pathway , 2022, Nutrients.

[7]  N. el-Guebaly,et al.  Pharmacotherapies for Adults With Alcohol Use Disorders: A Systematic Review and Network Meta-analysis , 2022, Journal of addiction medicine.

[8]  R. Abagyan,et al.  Discovery of Triple Inhibitors of Both SARS-CoV-2 Proteases and Human Cathepsin L , 2022, Pharmaceuticals.

[9]  Hao Tan,et al.  Invalidation of dieckol and 1,2,3,4,6-pentagalloylglucose (PGG) as SARS-CoV-2 main protease inhibitors and the discovery of PGG as a papain-like protease inhibitor , 2022, Medicinal Chemistry Research.

[10]  W. Xiao,et al.  Disulfiram Exerts Antifibrotic and Anti-Inflammatory Therapeutic Effects on Perimysial Orbital Fibroblasts in Graves’ Orbitopathy , 2022, International journal of molecular sciences.

[11]  M. Embers,et al.  Borreliella burgdorferi Antimicrobial-Tolerant Persistence in Lyme Disease and Posttreatment Lyme Disease Syndromes , 2022, mBio.

[12]  R. F. Cardoso,et al.  A systematic review of disulfiram as an antibacterial agent: What is the evidence? , 2022, International journal of antimicrobial agents.

[13]  M. Hörner,et al.  Repositioning of Disulfiram in Association with Vancomycin Against Enterococcus spp. MDR and XDR , 2022, Current Microbiology.

[14]  M. Harrison,et al.  Prospective clinical trial of disulfiram plus copper in men with metastatic castration‐resistant prostate cancer , 2022, The Prostate.

[15]  K. Sargsyan,et al.  From quantum‐derived principles underlying cysteine reactivity to combating the COVID‐19 pandemic , 2022, Wiley interdisciplinary reviews. Computational molecular science.

[16]  R. Agarwal Diffuse subendocardial ischemia secondary to disulfiram-alcohol ingestion , 2022, Indian Journal of Pharmacology.

[17]  H. M. Ali,et al.  SAR and QSAR of COVID-19 Main Protease–Inhibitor Interactions of Recently X-ray Crystalized Complexes , 2022, Proceedings of the National Academy of Sciences, India Section B: Biological Sciences.

[18]  P. Sun,et al.  Disulfiram attenuates MCMV-Induced pneumonia by inhibition of NF-κB/NLRP3 signaling pathway in immunocompromised mice. , 2021, International immunopharmacology.

[19]  T. Long,et al.  Pharmacological evaluation of disulfiram analogs as antimicrobial agents and their application as inhibitors of fosB-mediated fosfomycin resistance , 2022, The Journal of Antibiotics.

[20]  M. Zhang,et al.  Disulfiram Enhances the Activity of Polymyxin B Against Klebsiella pneumoniae by Inhibiting Lipid A Modification , 2022, Infection and drug resistance.

[21]  M. Hung,et al.  Disulfiram blocked cell entry of SARS-CoV-2 via inhibiting the interaction of spike protein and ACE2. , 2022, American journal of cancer research.

[22]  OUP accepted manuscript , 2022, Journal of Antimicrobial Chemotherapy.

[23]  Z. Gu,et al.  Leveraging disulfiram to treat cancer: Mechanisms of action, delivery strategies, and treatment regimens. , 2021, Biomaterials.

[24]  W. Xiao,et al.  Disulfiram exerts antiadipogenic, anti-inflammatory, and antifibrotic therapeutic effects in an in vitro model of Graves' orbitopathy. , 2021, Thyroid : official journal of the American Thyroid Association.

[25]  Yongzhuo Huang,et al.  Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases , 2021, Acta Pharmacologica Sinica.

[26]  Zhenming Gao,et al.  Wedelolactone alleviates acute pancreatitis and associated lung injury via GPX4 mediated suppression of pyroptosis and ferroptosis. , 2021, Free radical biology & medicine.

[27]  S. Frankl,et al.  Devastating Neurological Injury as a Result of Treatment of "Chronic Lyme Disease". , 2021, Mayo Clinic proceedings.

[28]  Suwen Zhao,et al.  A computational evaluation of targeted oxidation strategy (TOS) for potential inhibition of SARS-CoV-2 by disulfiram and analogues , 2021, Biophysical Chemistry.

[29]  Natasha Khan,et al.  Methaemoglobinaemia Secondary to Disulfiram. , 2021, Alcohol and alcoholism.

[30]  Shaoyong Lu,et al.  Mechanism of zinc ejection by disulfiram in nonstructural protein 5A. , 2021, Physical chemistry chemical physics : PCCP.

[31]  D. Sulejczak,et al.  Advantages and disadvantages of disulfiram coadministered with popular addictive substances. , 2021, European journal of pharmacology.

[32]  S. Buys,et al.  A Phase 1 dose-escalation study of disulfiram and copper gluconate in patients with advanced solid tumors involving the liver using S-glutathionylation as a biomarker , 2021, BMC cancer.

[33]  Ruicheng Zhang,et al.  Disulfiram inhibits inflammation and fibrosis in a rat unilateral ureteral obstruction model by inhibiting gasdermin D cleavage and pyroptosis , 2021, Inflammation Research.

[34]  K. Sargsyan,et al.  Synergistic Inhibition of SARS-CoV-2 Replication Using Disulfiram/Ebselen and Remdesivir , 2021, ACS pharmacology & translational science.

[35]  S. Moonah,et al.  Drug Repurposing of the Alcohol Abuse Medication Disulfiram as an Anti-Parasitic Agent , 2021, Frontiers in Cellular and Infection Microbiology.

[36]  M. Mendes,et al.  Disulfiram-induced epileptic seizures , 2021, BMJ Case Reports.

[37]  Tian Lan,et al.  Co-treatment with disulfiram and glycyrrhizic acid suppresses the inflammatory response of chondrocytes , 2021, Journal of Orthopaedic Surgery and Research.

[38]  Chen Lu,et al.  Disulfiram: a novel repurposed drug for cancer therapy , 2021, Cancer Chemotherapy and Pharmacology.

[39]  A. Tatu,et al.  Disulfiram-Induced Baboon Syndrome. , 2020, American Journal of Therapeutics.

[40]  Jiachen Gao,et al.  “Repurposing” Disulfiram in the Treatment of Lyme Disease and Babesiosis: Retrospective Review of First 3 Years’ Experience in One Medical Practice , 2020, Antibiotics.

[41]  D. Basu,et al.  Disulfiram Ethanol Reaction with Alcohol-Based Hand Sanitizer: An Exploratory Study , 2020, Alcohol and alcoholism.

[42]  Chunlong Ma,et al.  Ebselen, Disulfiram, Carmofur, PX-12, Tideglusib, and Shikonin Are Nonspecific Promiscuous SARS-CoV-2 Main Protease Inhibitors , 2020, ACS pharmacology & translational science.

[43]  N. Madrid-Elena,et al.  Maraviroc reactivates HIV with potency similar to that of other latency reversing drugs without inducing toxicity in CD8 T cells. , 2020, Biochemical pharmacology.

[44]  W. Shi,et al.  Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations against Stationary Phase Borrelia burgdorferi , 2020, Antibiotics.

[45]  Ying Peng,et al.  Efficacy of pharmacotherapeutics for patients comorbid with alcohol use disorders and depressive symptoms—A bayesian network meta‐analysis , 2020, CNS neuroscience & therapeutics.

[46]  E. Streel,et al.  Is Alcohol in Hand Sanitizers Absorbed Through the Skin or Lungs? Implications for Disulfiram Treatment , 2020, Alcohol and Alcoholism.

[47]  A. De Sousa Disulfiram Ethanol Reaction in a Patient Abstinent from Alcohol Caused by Hand Sanitizing. , 2020, Alcohol and alcoholism.

[48]  Naún Lobo-Galo,et al.  FDA-approved thiol-reacting drugs that potentially bind into the SARS-CoV-2 main protease, essential for viral replication , 2020, Journal of biomolecular structure & dynamics.

[49]  K. Sargsyan,et al.  Multi-targeting of functional cysteines in multiple conserved SARS-CoV-2 domains by clinically safe Zn-ejectors† , 2020, Chemical science.

[50]  Chunfu Wu,et al.  The combination of disulfiram and copper for cancer treatment. , 2020, Drug discovery today.

[51]  J. Mahadevan,et al.  Cerebral Watershed Infarcts Due to Disulfiram-Ethanol Reaction. , 2020, The Primary Care Companion For CNS Disorders.

[52]  J. Lieberman,et al.  FDA-approved disulfiram inhibits pyroptosis by blocking gasdermin D pore formation , 2020, Nature Immunology.

[53]  P. Sun,et al.  Disulfiram suppresses NLRP3 inflammasome activation to treat peritoneal and gouty inflammation. , 2020, Free radical biology & medicine.

[54]  Alison W. Rebman,et al.  Post-treatment Lyme Disease as a Model for Persistent Symptoms in Lyme Disease , 2020, Frontiers in Medicine.

[55]  T. Mark,et al.  Survey of Addiction Specialists’ Use of Medications to Treat Alcohol Use Disorder , 2020, Frontiers in Psychiatry.

[56]  Ke-Wu Yang,et al.  Disulfiram as a potent metallo-β-lactamase inhibitor with dual functional mechanisms. , 2020, Chemical communications.

[57]  D. Gomez,et al.  New drugs are not enough-drug repositioning in oncology: An update , 2020, International journal of oncology.

[58]  D. Younger,et al.  Antabuse for Lyme Disease: The Way Forward , 2020, World Journal of Neuroscience.

[59]  L. Trombetta,et al.  Comparative effects of Mancozeb and Disulfiram-induced striated muscle myopathies in Long-Evans rats. , 2019, Environmental toxicology and pharmacology.

[60]  M. Inayathullah,et al.  Repurposing Disulfiram (Tetraethylthiuram Disulfide) as a Potential Drug Candidate against Borrelia burgdorferi In Vitro and In Vivo , 2019, bioRxiv.

[61]  B. Albensi What Is Nuclear Factor Kappa B (NF-κB) Doing in and to the Mitochondrion? , 2019, Front. Cell Dev. Biol..

[62]  Sander K. Govers,et al.  Borrelia burgdorferi peptidoglycan is a persistent antigen in patients with Lyme arthritis , 2019, Proceedings of the National Academy of Sciences.

[63]  K. Liegner Disulfiram (Tetraethylthiuram Disulfide) in the Treatment of Lyme Disease and Babesiosis: Report of Experience in Three Cases , 2019, Antibiotics.

[64]  T. Kosten,et al.  Pharmacogenetic role of dopamine transporter (SLC6A3) variation on response to disulfiram treatment for cocaine addiction. , 2019, The American journal on addictions.

[65]  Q. Dou,et al.  Repurposing Disulfiram as an Anti-Cancer Agent: Updated Review on Literature and Patents. , 2019, Recent patents on anti-cancer drug discovery.

[66]  R. Kaufman,et al.  Disulfiram (Antabuse) Activates ROS-Dependent ER Stress and Apoptosis in Oral Cavity Squamous Cell Carcinoma , 2019, Journal of clinical medicine.

[67]  K. Fink,et al.  A multicenter phase II study of temozolomide plus disulfiram and copper for recurrent temozolomide-resistant glioblastoma , 2019, Journal of Neuro-Oncology.

[68]  Houhui Song,et al.  Recent advances in the mechanisms of NLRP3 inflammasome activation and its inhibitors , 2019, Cell Death & Disease.

[69]  Kentaro Kato,et al.  Repurposing existing drugs: identification of irreversible IMPDH inhibitors by high-throughput screening , 2018, Journal of enzyme inhibition and medicinal chemistry.

[70]  T. Long,et al.  Antibacterial activity of disulfiram and its metabolites , 2018, Journal of applied microbiology.

[71]  S. Lewin,et al.  Population Pharmacokinetics and Pharmacodynamics of Disulfiram on Inducing Latent HIV‐1 Transcription in a Phase IIb Trial , 2018, Clinical pharmacology and therapeutics.

[72]  Xing Tang,et al.  Disulfiram-loaded mixed nanoparticles with high drug-loading and plasma stability by reducing the core crystallinity for intravenous delivery. , 2018, Journal of colloid and interface science.

[73]  W. Geldenhuys,et al.  Disulfiram-based disulfides as narrow-spectrum antibacterial agents. , 2018, Bioorganic & medicinal chemistry letters.

[74]  Rudrarpan Chatterjee,et al.  Fulminant encephalopathy with unusual brain imaging in disulfiram toxicity , 2018, Neurology.

[75]  S. Reinhardt,et al.  Identification of disulfiram as a secretase-modulating compound with beneficial effects on Alzheimer’s disease hallmarks , 2018, Scientific Reports.

[76]  S. Lewin,et al.  Getting the "Kill" into "Shock and Kill": Strategies to Eliminate Latent HIV. , 2018, Cell host & microbe.

[77]  J. Yager,et al.  The American Psychiatric Association Practice Guideline for the Pharmacological Treatment of Patients With Alcohol Use Disorder. , 2018, The American journal of psychiatry.

[78]  C. Chou,et al.  Disulfiram can inhibit MERS and SARS coronavirus papain-like proteases via different modes , 2017, Antiviral Research.

[79]  Jiri Bartek,et al.  Alcohol-abuse drug disulfiram targets cancer via p97 segregase adapter NPL4 , 2017, Nature.

[80]  S. Sarkar,et al.  Disulfiram induced psychosis: Revisiting an age-old entity. , 2017, Asian journal of psychiatry.

[81]  Harry D J Knights A Critical Review of the Evidence Concerning the HIV Latency Reversing Effect of Disulfiram, the Possible Explanations for Its Inability to Reduce the Size of the Latent Reservoir In Vivo, and the Caveats Associated with Its Use in Practice , 2017, AIDS research and treatment.

[82]  Y. Liu,et al.  Poly lactic-co-glycolic acid controlled delivery of disulfiram to target liver cancer stem-like cells , 2017, Nanomedicine : nanotechnology, biology, and medicine.

[83]  T. Santos,et al.  Sensory-motor axonal polyneuropathy involving cranial nerves: An uncommon manifestation of disulfiram toxicity , 2017, Clinical Neurology and Neurosurgery.

[84]  I. Ozerol,et al.  Disulfiram, as a candidate NF-κB and proteasome inhibitor, prevents endometriotic implant growing in a rat model of endometriosis. , 2016, European review for medical and pharmacological sciences.

[85]  G. Addolorato,et al.  Treatment of alcohol use disorders in patients with alcoholic liver disease. , 2016, Journal of hepatology.

[86]  Sara R. Jones,et al.  Cocaine Self-Administration Produces Long-Lasting Alterations in Dopamine Transporter Responses to Cocaine , 2016, The Journal of Neuroscience.

[87]  W. Shi,et al.  A Drug Combination Screen Identifies Drugs Active against Amoxicillin-Induced Round Bodies of In Vitro Borrelia burgdorferi Persisters from an FDA Drug Library , 2016, Front. Microbiol..

[88]  M. Parekh,et al.  Identification of new drug candidates against Borrelia burgdorferi using high-throughput screening , 2016, Drug design, development and therapy.

[89]  R. Rison,et al.  Disulfiram neuropathy: two case reports , 2016, Journal of Medical Case Reports.

[90]  C. Lim,et al.  Using an Old Drug to Target a New Drug Site: Application of Disulfiram to Target the Zn-Site in HCV NS5A Protein. , 2016, Journal of the American Chemical Society.

[91]  Xuesi Chen,et al.  Stable loading and delivery of disulfiram with mPEG-PLGA/PCL mixed nanoparticles for tumor therapy. , 2016, Nanomedicine : nanotechnology, biology, and medicine.

[92]  C. Cardozo,et al.  The Ubiquitin-Proteasome System: Potential Therapeutic Targets for Alzheimer’s Disease and Spinal Cord Injury , 2016, Front. Mol. Neurosci..

[93]  T. H. Ferreira-Vieira,et al.  Alzheimer's Disease: Targeting the Cholinergic System , 2016, Current neuropharmacology.

[94]  A. Renslo,et al.  Antileishmanial Activity of Disulfiram and Thiuram Disulfide Analogs in an Ex Vivo Model System Is Selectively Enhanced by the Addition of Divalent Metal Ions , 2015, Antimicrobial Agents and Chemotherapy.

[95]  M. Jagadeesh,et al.  Disulfiram-induced seizures with convulsions in a young male patient: A case study , 2015, Indian Journal of Psychiatry.

[96]  K. Lewis,et al.  Borrelia burgdorferi, the Causative Agent of Lyme Disease, Forms Drug-Tolerant Persister Cells , 2015, Antimicrobial Agents and Chemotherapy.

[97]  C. King,et al.  Parasitism in Children Aged Three Years and Under: Relationship between Infection and Growth in Rural Coastal Kenya , 2015, PLoS neglected tropical diseases.

[98]  T. Peretz,et al.  A phase IIb trial assessing the addition of disulfiram to chemotherapy for the treatment of metastatic non-small cell lung cancer. , 2015, The oncologist.

[99]  R. Sagar,et al.  Tracing the journey of disulfiram: From an unintended discovery to a treatment option for alcoholism , 2015 .

[100]  F. Tuna,et al.  On the interaction of copper(II) with disulfiram. , 2014, Chemical communications.

[101]  R. Siliciano,et al.  A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. , 2014, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[102]  Catherine Z. Chen,et al.  Structural Basis for Inactivation of Giardia lamblia Carbamate Kinase by Disulfiram* , 2014, The Journal of Biological Chemistry.

[103]  C. Supuran,et al.  Dithiocarbamates strongly inhibit the β-class carbonic anhydrases from Mycobacterium tuberculosis , 2013, Journal of enzyme inhibition and medicinal chemistry.

[104]  L. Baldaçara,et al.  Could disulfiram be a new treatment for crack cocaine dependence?: a pilot study. , 2013, Revista brasileira de psiquiatria.

[105]  Catherine Z. Chen,et al.  A Homogenous Luminescence Assay Reveals Novel Inhibitors for Giardia Lamblia Carbamate Kinase , 2012, Current chemical genomics.

[106]  X. Bian,et al.  Cytotoxic effect of disulfiram/copper on human glioblastoma cell lines and ALDH-positive cancer-stem-like cells , 2012, British Journal of Cancer.

[107]  S. Yip,et al.  Disulfiram, a drug widely used to control alcoholism, suppresses self-renewal of glioblastoma and overrides resistance to temozolomide , 2012, Oncotarget.

[108]  T. Roskams,et al.  EASL clinical practical guidelines: management of alcoholic liver disease. , 2012, Journal of hepatology.

[109]  L. Bockenstedt,et al.  Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. , 2012, The Journal of clinical investigation.

[110]  Vindhya Koppaka,et al.  Aldehyde Dehydrogenase Inhibitors: a Comprehensive Review of the Pharmacology, Mechanism of Action, Substrate Specificity, and Clinical Application , 2012, Pharmacological Reviews.

[111]  L. Kremer,et al.  Antitubercular Activity of Disulfiram, an Antialcoholism Drug, against Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Isolates , 2012, Antimicrobial Agents and Chemotherapy.

[112]  P. Ray,et al.  Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. , 2012, Cellular signalling.

[113]  S. Narasimhan,et al.  Correction: Persistence of Borrelia burgdorferi in Rhesus Macaques following Antibiotic Treatment of Disseminated Infection , 2012, PLoS ONE.

[114]  R. Siliciano,et al.  Disulfiram Reactivates Latent HIV-1 in a Bcl-2-Transduced Primary CD4+ T Cell Model without Inducing Global T Cell Activation , 2011, Journal of Virology.

[115]  Y. Hori,et al.  Anti-inflammatory potency of oral disulfiram compared with dexamethasone on endotoxin-induced uveitis in rats. , 2011, The Journal of veterinary medical science.

[116]  D. Buac,et al.  Disulfiram, and disulfiram derivatives as novel potential anticancer drugs targeting the ubiquitin-proteasome system in both preclinical and clinical studies. , 2011, Current cancer drug targets.

[117]  L. Kremer,et al.  Synthesis and evaluation of anti-tubercular activity of new dithiocarbamate sugar derivatives. , 2011, Bioorganic & medicinal chemistry letters.

[118]  A. Renslo,et al.  Identification of Small Molecule Lead Compounds for Visceral Leishmaniasis Using a Novel Ex Vivo Splenic Explant Model System , 2011, PLoS neglected tropical diseases.

[119]  P. Holmes,et al.  Disulfiram Attenuates Drug-Primed Reinstatement of Cocaine Seeking via Inhibition of Dopamine β-Hydroxylase , 2010, Neuropsychopharmacology.

[120]  K. Barth,et al.  Disulfiram: an old therapeutic with new applications. , 2010, CNS & neurological disorders drug targets.

[121]  John S. Lazo,et al.  Identification of Potent Chemotypes Targeting Leishmania major Using a High-Throughput, Low-Stringency, Computationally Enhanced, Small Molecule Screen , 2009, PLoS neglected tropical diseases.

[122]  D. Weinshenker,et al.  mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. , 2009, Molecular interventions.

[123]  S. K. Choudhuri,et al.  The role of copper in drug-resistant murine and human tumors , 2009, BioMetals.

[124]  S. Barthold,et al.  Persistence of Borrelia burgdorferi following Antibiotic Treatment in Mice , 2008, Antimicrobial Agents and Chemotherapy.

[125]  Nihal Ahmad,et al.  Dose translation from animal to human studies revisited , 2007, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[126]  H. Kragh FROM DISULFIRAM TO ANTABUSE: THE INVENTION OF A DRUG , 2008 .

[127]  M. Ceylan,et al.  Manic episode with psychotic symptoms associated with high dose of disulfiram: a case report. , 2007, Journal of clinical psychopharmacology.

[128]  P. Jatlow,et al.  Disulfiram effects on responses to intravenous cocaine administration. , 2007, Drug and alcohol dependence.

[129]  J. Daeppen,et al.  Neuropathie optique lors d’un traitement par disulfirame , 2006 .

[130]  Jesse J. Suh,et al.  The Status of Disulfiram: A Half of a Century Later , 2006, Journal of clinical psychopharmacology.

[131]  K. Borden,et al.  Arenavirus Z protein as an antiviral target: virus inactivation and protein oligomerization by zinc finger-reactive compounds. , 2006, The Journal of general virology.

[132]  Ashima Sharma Disulfiram and low nickel diet in the management of hand eczema: a clinical study. , 2006, Indian journal of dermatology, venereology and leprology.

[133]  B. Rounsaville,et al.  Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: a randomized placebo-controlled trial. , 2004, Archives of general psychiatry.

[134]  R. Fuller,et al.  Does disulfiram have a role in alcoholism treatment today? , 2004, Addiction.

[135]  B. Johansson,et al.  Inhibition of erythrocyte aldehyde dehydrogenase activity and elimination kinetics of diethyldithiocarbamic acid methyl ester and its monothio analogue after administration of single and repeated doses of disulfiram to man , 2004, European Journal of Clinical Pharmacology.

[136]  Stephen Naylor,et al.  Determination of in vivo adducts of disulfiram with mitochondrial aldehyde dehydrogenase. , 2001, Biochemical pharmacology.

[137]  R. Anton,et al.  Pharmacologic approaches to the management of alcoholism. , 2001, The Journal of clinical psychiatry.

[138]  Stephen Naylor,et al.  Role of disulfiram in the in vitro inhibition of rat liver mitochondrial aldehyde dehydrogenase. , 2000, Biochemical pharmacology.

[139]  T. George,et al.  Disulfiram versus placebo for cocaine dependence in buprenorphine-maintained subjects: a preliminary trial , 2000, Biological Psychiatry.

[140]  Stephen Naylor,et al.  Identification of the protein-drug adduct formed between aldehyde dehydrogenase and S-methyl-N,N-diethylthiocarbamoyl sulfoxide by on-line proteolytic digestion high performance liquid chromatography electrospray ionization mass spectrometry. , 2000, Rapid communications in mass spectrometry : RCM.

[141]  E. Kharasch,et al.  Lack of single-dose disulfiram effects on cytochrome P-450 2C9, 2C19, 2D6, and 3A4 activities: evidence for specificity toward P-450 2E1. , 1999, Drug metabolism and disposition: the biological fate of chemicals.

[142]  J. Chick Safety Issues Concerning the Use of Disulfiram in Treating Alcohol Dependence , 1999, Drug safety.

[143]  A. Tomlinson,et al.  Inhibition of human mitochondrial aldehyde dehydrogenase by metabolites of disulfiram and structural characterization of the enzyme adduct by HPLC-tandem mass spectrometry. , 1999, Advances in experimental medicine and biology.

[144]  A. Tomlinson,et al.  Inhibition of human mitochondrial aldehyde dehydrogenase by the disulfiram metabolite S-methyl-N,N-diethylthiocarbamoyl sulfoxide: structural characterization of the enzyme adduct by HPLC-tandem mass spectrometry. , 1997, Biochemical pharmacology.

[145]  T. Baillie,et al.  Studies on the metabolic activation of disulfiram in rat. Evidence for electrophilic S-oxygenated metabolites as inhibitors of aldehyde dehydrogenase and precursors of urinary N-acetylcysteine conjugates. , 1997, The Journal of pharmacology and experimental therapeutics.

[146]  J. Hughes,et al.  The efficacy of disulfiram: a review of outcome studies. , 1997, Addiction.

[147]  K. Murthy Psychosis during disulfiram therapy for alcoholism. , 1997, Journal of the Indian Medical Association.

[148]  X. Forns,et al.  Disulfiram-induced hepatitis. Report of four cases and review of the literature. , 1994, Journal of hepatology.

[149]  D. Jaeck,et al.  Sodium ditiocarb as adjuvant immunotherapy for high risk breast cancer: A randomized study , 1993, Biotherapy.

[150]  B. Johansson A review of the pharmacokinetics and pharmacodynamics of disulfiram and its metabolites , 1992, Acta psychiatrica Scandinavica. Supplementum.

[151]  S. Loft,et al.  Disulfiram therapy –adverse drug reactions and interactions , 1992, Acta psychiatrica Scandinavica. Supplementum.

[152]  D. Männel,et al.  Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells , 1992, The Journal of experimental medicine.

[153]  P. Gessner,et al.  Disulfiram and its Metabolite, Diethyldithiocarbamate , 1992, Springer Netherlands.

[154]  M. Orsetti,et al.  Action of a chronic disulfiram administration on memory decay and on central cholinergic and adrenergic systems , 1991, Brain Research.

[155]  B. Johansson,et al.  Dose-effect relationship of disulfiram in human volunteers. II: A study of the relation between the disulfiram-alcohol reaction and plasma concentrations of acetaldehyde, diethyldithiocarbamic acid methyl ester, and erythrocyte aldehyde dehydrogenase activity. , 1991, Pharmacology & toxicology.

[156]  J. Eaton,et al.  Antimalarial activity of diethyldithiocarbamate. Potentiation by copper. , 1990, Biochemical pharmacology.

[157]  J. Maroun,et al.  A Randomized Phase II Study of Cisplatin Alone Versus Cisplatin Plus Disulfiram , 1990, American journal of clinical oncology.

[158]  P. Gøtzsche,et al.  Lack of immunomodulating effect of disulfiram on HIV positive patients. , 1990, International journal of immunopharmacology.

[159]  R. Berlin Disulfiram hepatotoxicity: a consideration of its mechanism and clinical spectrum. , 1989, Alcohol and alcoholism.

[160]  C. Trépo,et al.  RANDOMISED, DOUBLE-BLIND, PLACEBO-CONTROLLED TRIAL OF DITIOCARB SODIUM ('IMUTHIOL') IN HUMAN IMMUNODEFICIENCY VIRUS INFECTION , 1988, The Lancet.

[161]  K. Lee,et al.  Psychiatric complications of disulfiram treatment. , 1987, The American journal of psychiatry.

[162]  F. Iber,et al.  Liver toxicity encountered in the Veterans Administration trial of disulfiram in alcoholics. , 1987, Alcoholism, clinical and experimental research.

[163]  R. Mcpherson,et al.  Serum albumin and the metabolism of disulfiram. , 1986, Biochemical pharmacology.

[164]  F. Iber,et al.  Disulfiram Treatment of Alcoholism: A Veterans Administration Cooperative Study , 1986 .

[165]  D. Mays,et al.  Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics , 1986, Clinical pharmacology and therapeutics.

[166]  B. Johansson Rapid and sensitive on-line precolumn purification and high-performance liquid chromatographic assay for disulfiram and its metabolites. , 1986, Journal of chromatography.

[167]  M. D. Faiman,et al.  Elimination kinetics of disulfiram in alcoholics after single and repeated doses , 1984, Clinical pharmacology and therapeutics.

[168]  C. Brewer How Effective is the Standard Dose of Disulfiram? A Review of the Alcohol-Disulfiram Reaction in Practice , 1984, British Journal of Psychiatry.

[169]  T. Keane,et al.  Spouse contracting to increase antabuse compliance in alcoholic veterans. , 1984, Journal of clinical psychology.

[170]  P. Hougaard,et al.  Treatment of nickel dermatitis with Antabuse® a double blind study , 1983, Contact dermatitis.

[171]  T. Worner Peripheral neuropathy after disulfiram administration: reversibility despite continued therapy. , 1982, Drug and alcohol dependence.

[172]  B. Andresen,et al.  The Actions and Metabolic Fate of Disulfiram , 1981 .

[173]  T. Marra Disulfiram neuropathy. , 1981, Wisconsin medical journal.

[174]  M. D. Faiman,et al.  Disulfiram distribution and elimination in the rat after oral and intraperitoneal administration. , 1980, Alcoholism, clinical and experimental research.

[175]  W. Trager,et al.  Tetraethylthiuram disulfide (Antabuse) inhibits the human malaria parasite Plasmodium falciparum. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[176]  J. C. Tjell,et al.  Antabuse® treatment of nickel dermatitis. Chelation – a new principle in the treatment of nickel dermatitis , 1979, Contact dermatitis.

[177]  W. Davidson,et al.  Determination of Nanogram Quantities of Disulfiram in Human and Rat Plasma by Gas—Liquid Chromatography , 1979 .

[178]  J. Williamson,et al.  Trypanocidal Activity of Antitumor Antibiotics and Other Metabolic Inhibitors , 1978, Antimicrobial Agents and Chemotherapy.

[179]  J. Cobby,et al.  The rapid reduction of disulfiram in blood and plasma. , 1977, The Journal of pharmacology and experimental therapeutics.

[180]  G. Cohen,et al.  In vivo inhibition of superoxide dismutase in mice by diethyldithiocarbamate. , 1976, The Journal of biological chemistry.

[181]  J. Langston,et al.  Disulfiram-induced encephalopathy. , 1976, Archives of neurology.

[182]  G. Cross,et al.  Utilization of amino acids by Trypanosoma brucei in culture: L-threonine as a precursor for acetate , 1975, Parasitology.

[183]  C. Rosenberg,et al.  Disulfiram maintenance in outpatient treatment of alcoholism. , 1973, Archives of general psychiatry.

[184]  M. Jakubowski,et al.  Diethyldithiocarbamic acid methyl ester. A metabolite of disulfiram. , 1972, Biochemical pharmacology.

[185]  J. Gillette,et al.  Disulfiram impairment of drug metabolism by rat liver microsomes. , 1969, The Journal of pharmacology and experimental therapeutics.

[186]  A. Hulanicki Complexation reactions of dithiocarbamates. , 1967, Talanta.

[187]  R. Satran,et al.  Disulfiram (Antabuse) psychosis. , 1967, The American journal of psychiatry.

[188]  C. D. Johnston,et al.  The in vivo production of carbon disulfide from tetraethylthiuramdisulfide (antabuse). , 1953, Biochimica et biophysica acta.

[189]  E. Jacobsen,et al.  A drug sensitizing the organism to ethyl alcohol. , 1948, Lancet.