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Identification
NameDisulfiram
Accession NumberDB00822  (APRD00767)
TypeSmall Molecule
GroupsApproved
Description

A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase. [PubChem]

Structure
Thumb
Synonyms
1,1'-dithiobis(N,N-diethylthioformamide)
Antabuse (tn)
Bis(diethylthiocarbamoyl) disulfide
Disulfiram
N,N,N',N'-tetraethylthiuram disulfide
Tetraethylthioperoxydicarbonic Diamide
Tetraethylthiuram Disulfide
Tetraethylthiuram Disulphide
External Identifiers
  • Dupon 4472
  • Dupont Fungicide 4472
  • USAF B-33
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Antabuse Tab 0.25gmtablet250 mgoralAyerst Laboratories1966-12-311996-09-10Canada
Antabuse Tab 250mgtablet250 mgoralWyeth Ayerst Canada Inc.1994-12-312001-05-07Canada
Antabuse Tab 500mgtablet500 mgoralWyeth Ayerst Canada Inc.1994-12-312001-05-07Canada
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Antabusetablet250 mg/1oralPhysicians Total Care, Inc.2004-03-30Not applicableUs
Antabusetablet500 mg/1oralTeva Women's Health, Inc.2006-02-01Not applicableUs
Antabusetablet250 mg/1oralTeva Women's Health, Inc.2000-12-01Not applicableUs
Disulfiramtablet250 mg/1oralAlvogen Inc.2012-08-31Not applicableUs
Disulfiramtablet250 mg/1oralRoxane Laboratories, Inc2014-11-04Not applicableUs
Disulfiramtablet250 mg/1oralCarilion Materials Management2011-04-01Not applicableUs
Disulfiramtablet250 mg/1oralQualitest Pharmaceuticals2012-12-31Not applicableUs
Disulfiramtablet500 mg/1oralRising Pharmaceuticals, Inc.2011-04-01Not applicableUs
Disulfiramtablet500 mg/1oralQualitest Pharmaceuticals2012-12-31Not applicableUs
Disulfiramtablet250 mg/1oralRising Pharmaceuticals, Inc.2011-04-01Not applicableUs
Disulfiramtablet500 mg/1oralMylan Pharmaceuticals Inc.2015-03-04Not applicableUs
Disulfiramtablet250 mg/1oralGolden State Medical Supply, Inc.2013-09-11Not applicableUs
Disulfiramtablet250 mg/1oralMylan Pharmaceuticals Inc.2015-03-04Not applicableUs
Disulfiramtablet500 mg/1oralTeva Pharmaceuticals USA Inc2011-07-19Not applicableUs
Disulfiramtablet250 mg/1oralTeva Pharmaceuticals USA Inc2011-04-15Not applicableUs
Disulfiramtablet500 mg/1oralRoxane Laboratories, Inc2014-11-04Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AntabusActavis
AntaethylSanofi
AntalcolSintofarm
AnticolPolfa Warszawa
AntietanolSanofi
ChronolCharoon Bhesaj
EsperalSanofi
Brand mixturesNot Available
SaltsNot Available
Categories
UNIITR3MLJ1UAI
CAS number97-77-8
WeightAverage: 296.539
Monoisotopic: 296.05093141
Chemical FormulaC10H20N2S4
InChI KeyInChIKey=AUZONCFQVSMFAP-UHFFFAOYSA-N
InChI
InChI=1S/C10H20N2S4/c1-5-11(6-2)9(13)15-16-10(14)12(7-3)8-4/h5-8H2,1-4H3
IUPAC Name
N,N-diethyl[(diethylcarbamothioyl)disulfanyl]carbothioamide
SMILES
CCN(CC)C(=S)SSC(=S)N(CC)CC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as organic thiocarbonic acid derivatives. These are organic compounds containing the thiocarbonic acid structure or a derivative thereof.
KingdomOrganic compounds
Super ClassOrganosulfur compounds
ClassThiocarbonyl compounds
Sub ClassOrganic thiocarbonic acid derivatives
Direct ParentOrganic thiocarbonic acid derivatives
Alternative Parents
Substituents
  • Dithiocarbamic acid or derivatives
  • Tertiary amine
  • Thiocarbonic acid derivative
  • Organic disulfide
  • Sulfenyl compound
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment and management of chronic alcoholism
PharmacodynamicsDisulfiram produces a sensitivity to alcohol which results in a highly unpleasant reaction when the patient under treatment ingests even small amounts of alcohol. Disulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake, the concentration of acetaldehyde occurring in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. Accumulation of acetaldehyde in the blood produces a complex of highly unpleasant symptoms referred to hereinafter as the disulfiram-alcohol reaction. This reaction, which is proportional to the dosage of both disulfiram and alcohol, will persist as long as alcohol is being metabolized. Disulfiram does not appear to influence the rate of alcohol elimination from the body. Prolonged administration of disulfiram does not produce tolerance; the longer a patient remains on therapy, the more exquisitely sensitive he becomes to alcohol.
Mechanism of actionDisulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.
Related Articles
AbsorptionDisulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic.

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityLD50=8.6g/kg (orally in rats). Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.
Affected organisms
  • Humans and other mammals
Pathways
PathwayCategorySMPDB ID
Disulfiram Action PathwayDrug actionSMP00429
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9808
Blood Brain Barrier+0.9668
Caco-2 permeable+0.548
P-glycoprotein substrateNon-substrate0.71
P-glycoprotein inhibitor INon-inhibitor0.8236
P-glycoprotein inhibitor IINon-inhibitor0.9884
Renal organic cation transporterNon-inhibitor0.8379
CYP450 2C9 substrateNon-substrate0.8497
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7558
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorInhibitor0.8948
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5397
Ames testNon AMES toxic0.9132
CarcinogenicityCarcinogens 0.6989
BiodegradationNot ready biodegradable0.9767
Rat acute toxicity2.7419 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8617
hERG inhibition (predictor II)Non-inhibitor0.8823
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Odyssey pharmaceuticals inc
  • Par pharmaceutical inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg
Tabletoral500 mg
Tabletoral250 mg/1
Tabletoral500 mg/1
Prices
Unit descriptionCostUnit
Antabuse 500 mg tablet6.65USD tablet
Antabuse 250 mg tablet4.24USD tablet
Disulfiram powder1.92USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point71.5 °CPhysProp
boiling point117 °C at 1.70E+01 mm HgPhysProp
water solubility4.09 mg/L (at 25 °C)YALKOWSKY,SH & HE,Y (2003)
logP3.88HANSCH,C ET AL. (1995)
logS-4.86ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.0126 mg/mLALOGPS
logP3.88ALOGPS
logP4.16ChemAxon
logS-4.4ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count7ChemAxon
Refractivity88.24 m3·mol-1ChemAxon
Polarizability31.6 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.65 KB)
Spectra
Spectrum TypeDescriptionSplash Key
MSMass Spectrum (Electron Ionization)splash10-014r-9510000000-2e18f478f9c0f9a2958aView in MoNA
1D NMR1H NMR SpectrumNot Available
1D NMR13C NMR SpectrumNot Available
References
Synthesis Reference

Adams, H.S. and Meuser, L.; US.Patent 1,782,111; November 18,1930; assigned to The
Naugatuck Chemical Company.
Bailey, G.C.; U.S.Patent 1,796,977; March 17,1931; assigned to The Roessler & Hasslacher
Chemical Company.

General References
  1. Nash T, Rice WG: Efficacies of zinc-finger-active drugs against Giardia lamblia. Antimicrob Agents Chemother. 1998 Jun;42(6):1488-92. [PubMed:9624499 ]
  2. Bouma MJ, Snowdon D, Fairlamb AH, Ackers JP: Activity of disulfiram (bis(diethylthiocarbamoyl)disulphide) and ditiocarb (diethyldithiocarbamate) against metronidazole-sensitive and -resistant Trichomonas vaginalis and Tritrichomonas foetus. J Antimicrob Chemother. 1998 Dec;42(6):817-20. [PubMed:10052908 ]
  3. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. doi: 10.1124/mi.9.4.6. [PubMed:19720750 ]
External Links
ATC CodesN07BB01P03AA04P03AA54
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (50.6 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolThe serum concentration of Acenocoumarol can be increased when it is combined with Disulfiram.
AminophyllineThe serum concentration of Aminophylline can be increased when it is combined with Disulfiram.
AripiprazoleThe serum concentration of Aripiprazole can be increased when it is combined with Disulfiram.
AtazanavirThe therapeutic efficacy of Disulfiram can be decreased when used in combination with Atazanavir.
CarbocisteineThe risk or severity of adverse effects can be increased when Disulfiram is combined with Carbocisteine.
ChlordiazepoxideThe serum concentration of Chlordiazepoxide can be increased when it is combined with Disulfiram.
ChlorzoxazoneThe metabolism of Chlorzoxazone can be decreased when combined with Disulfiram.
DacarbazineThe metabolism of Dacarbazine can be decreased when combined with Disulfiram.
DiazepamThe serum concentration of Diazepam can be increased when it is combined with Disulfiram.
DicoumarolThe serum concentration of Dicoumarol can be increased when it is combined with Disulfiram.
EthanolThe risk or severity of adverse effects can be increased when Disulfiram is combined with Ethanol.
FosphenytoinThe serum concentration of Fosphenytoin can be increased when it is combined with Disulfiram.
IsofluraneThe metabolism of Isoflurane can be decreased when combined with Disulfiram.
IsoniazidThe risk or severity of adverse effects can be increased when Disulfiram is combined with Isoniazid.
LopinavirThe risk or severity of adverse effects can be increased when Lopinavir is combined with Disulfiram.
MetronidazoleThe risk or severity of adverse effects can be increased when Disulfiram is combined with Metronidazole.
NicotineThe metabolism of Nicotine can be decreased when combined with Disulfiram.
ParaldehydeThe serum concentration of Paraldehyde can be increased when it is combined with Disulfiram.
PhenytoinThe serum concentration of Phenytoin can be increased when it is combined with Disulfiram.
RitonavirThe risk or severity of adverse effects can be increased when Ritonavir is combined with Disulfiram.
SertralineThe risk or severity of adverse effects can be increased when Disulfiram is combined with Sertraline.
SevofluraneThe metabolism of Sevoflurane can be decreased when combined with Disulfiram.
TheophyllineThe serum concentration of Theophylline can be increased when it is combined with Disulfiram.
TinidazoleThe risk or severity of adverse effects can be increased when Tinidazole is combined with Disulfiram.
TipranavirThe risk or severity of adverse effects can be increased when Disulfiram is combined with Tipranavir.
TizanidineThe serum concentration of Tizanidine can be increased when it is combined with Disulfiram.
WarfarinThe serum concentration of Warfarin can be increased when it is combined with Disulfiram.
Food Interactions
  • Avoid alcohol for up to 14 days after treatment has been stopped.
  • Take without regard to meals.

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Electron carrier activity
Specific Function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular Weight:
56380.93 Da
References
  1. Mackenzie IS, Maki-Petaja KM, McEniery CM, Bao YP, Wallace SM, Cheriyan J, Monteith S, Brown MJ, Wilkinson IB: Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1891-5. Epub 2005 Jul 28. [PubMed:16051882 ]
  2. Ho MP, Yo CH, Liu CM, Chen CL, Lee CC: Refractive hypotension in a patient with disulfiram-ethanol reaction. Am J Med Sci. 2007 Jan;333(1):53-5. [PubMed:17220694 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
L-ascorbic acid binding
Specific Function:
Conversion of dopamine to noradrenaline.
Gene Name:
DBH
Uniprot ID:
P09172
Molecular Weight:
69064.45 Da
References
  1. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. doi: 10.1124/mi.9.4.6. [PubMed:19720750 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms.
Gene Name:
CYP2E1
Uniprot ID:
P05181
Molecular Weight:
56848.42 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenyto...
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Vitamin d3 25-hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Gene Name:
CYP3A5
Uniprot ID:
P20815
Molecular Weight:
57108.065 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
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Drug created on June 13, 2005 07:24 / Updated on April 13, 2016 10:45