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targets (2) enzymes (4)
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Identification
Name Disulfiram
Accession Number DB00822 (APRD00767)
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Disulfuram
  • Disulphuram
  • Dupon 4472
  • Dupont Fungicide 4472
  • TATD
  • TETD
  • Tetraethylthioperoxydicarbonic Diamide
  • Tetraethylthiram Disulfide
  • Tetraethylthiram Disulphide
  • Tetraethylthiuram
  • Tetraethylthiuram Disulfide
  • Tetraethylthiuram Disulphide
  • Tetraethylthiuram Sulfide
  • Tetraethylthiuran Disulfide
  • TTD
  • Usaf B-33
Brand names
  • Abstensil
  • Abstinil
  • Abstinyl
  • Accel Tet
  • Accel Tet-R
  • Akrochem Tetd
  • Alcophobin
  • Alk-Aubs
  • Ancazide Et
  • Antabus
  • Antabuse
  • Antadix
  • Antaenyl
  • Antaethan
  • Antaethyl
  • Antaetil
  • Antalcol
  • Antetan
  • Antethyl
  • Antetil
  • Anteyl
  • Anthethyl
  • Anti-Ethyl
  • Antiaethan
  • Anticol
  • Antietanol
  • Antietil
  • Antikol
  • Antivitium
  • Aversan
  • Averzan
  • Bonibal
  • Contralin
  • Contrapot
  • Cronetal
  • Dicupral
  • Disetil
  • Disulfan
  • Disulfram
  • Ekagom Dtet
  • Ekagom Teds
  • Ekagom Tetds
  • Ekaland Tetd
  • Ephorran
  • Espenal
  • Esperal
  • Etabus
  • Ethyl Thiram
  • Ethyl Thiudad
  • Ethyl Thiurad
  • Ethyl Tuads
  • Ethyl Tuads Rodform
  • Ethyl Tuex
  • Ethyldithiourame
  • Ethyldithiurame
  • Etyl Tuex
  • Exhoran
  • Exhorran
  • Gababentin
  • Hoca
  • Krotenal
  • Nocbin
  • Nocceler Tet
  • Nocceler Tet-G
  • Noxal
  • Perkacit Tetd
  • Perkait Tetd
  • Refusal
  • Ro-Sulfiram
  • Sanceler Tet
  • Sanceler Tet-G
  • Soxinol Tet
  • Stopaethyl
  • Stopethyl
  • Stopety
  • Stopetyl
  • Super Rodiatox
  • Tenurid
  • Tenutex
  • Tetidis
  • Tetradin
  • Tetradine
  • Tetraetil
  • Teturam
  • Teturamin
  • Thiocid
  • Thiophos
  • Thioscabin
  • Thireranide
  • Tillram
  • Tiuram
  • TTS
  • TTS X
Brand name mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Alcohol Deterrents
CAS number 97-77-8
Weight Average: 296.539
Monoisotopic: 296.050931410
Chemical Formula C10H20N2S4
InChI Key InChIKey=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
Plain Text
IUPAC Name
N,N-diethyl[(diethylcarbamothioyl)disulfanyl]carbothioamide
SMILES
CCN(CC)C(=S)SSC(=S)N(CC)CC
Plain Text
Mass Spec show (8.6 KB)
Taxonomy
Kingdom Organic
Classes
  • Organic Disulfides
Substructures
  • Organic Disulfides
Pharmacology
Indication For the treatment and management of chronic alcoholism
Pharmacodynamics Disulfiram 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 action Disulfiram 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.
Absorption Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).
Volume of distribution Not Available
Protein binding Not Available
Metabolism

Hepatic.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity LD50=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
Pathway Name SMPDB ID
Smp00429 Disulfiram Pathway SMP00429
Pharmacoeconomics
Manufacturers
  • Odyssey pharmaceuticals inc
  • Par pharmaceutical inc
  • Watson laboratories inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Antabuse 500 mg tablet 6.65 USD tablet
Antabuse 250 mg tablet 4.24 USD tablet
Disulfiram powder 1.92 USD g
Patents Not Available
Properties
State solid
Melting point 71.5 oC
Experimental Properties
Property Value Source
water solubility 4.09 mg/L PhysProp
logP 1.9 PhysProp
logS -4.86 [ADME Research, USCD] PhysProp
Predicted Properties
Property Value Source
water solubility 1.26e-02 g/l ALOGPS
logP 3.88 ALOGPS
logP 4.16 ChemAxon Molconvert
logS -4.37 ALOGPS
pKa ChemAxon Molconvert
hydrogen acceptor count 0 ChemAxon Molconvert
hydrogen donor count 0 ChemAxon Molconvert
polar surface area 6.48 ChemAxon Molconvert
rotatable bond count 7 ChemAxon Molconvert
refractivity 88.24 ChemAxon Molconvert
polarizability 31.60 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Nash T, Rice WG: Efficacies of zinc-finger-active drugs against Giardia lamblia. Antimicrob Agents Chemother. 1998 Jun;42(6):1488-92. Pubmed
  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
  3. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. Pubmed 19720750
External Links
Resource Link
KEGG Drug D00131 Link_out
KEGG Compound C01692 Link_out
PubChem Compound 3117 Link_out
PubChem Substance 46506008 Link_out
ChemSpider 3005 Link_out
ChEBI 4659 Link_out
ChEMBL 4659 Link_out
Therapeutic Targets Database DAP000012 Link_out
PharmGKB PA449376 Link_out
Drug Product Database 2534 Link_out
RxList http://www.rxlist.com/cgi/generic/disulfiram.htm Link_out
Drugs.com http://www.drugs.com/cdi/disulfiram.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Disulfiram Link_out
ATC Codes
  • N07BB01
  • P03AA04
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS show (50.6 KB)
Interactions
Drug Interactions Not Available
Food Interactions
  • Avoid alcohol for up to 14 days after treatment has been stopped.
  • Take without regard to meals.
Targets

1. Aldehyde dehydrogenase, mitochondrial

Pharmacological action: yes
Actions: inhibitor
Organism class: human
UniProt ID: P05091 Link_out
Gene: ALDH2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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

2. Dopamine beta-hydroxylase

Pharmacological action: yes
Actions: inhibitor

Conversion of dopamine to noradrenaline

Organism class: human
UniProt ID: P09172 Link_out
Gene: DBH Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed *
Enzymes

1. Cytochrome P450 2E1

Actions: inhibitor

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

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. 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. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 2C9

Actions: inhibitor

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, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A4

Actions: substrate

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 xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on November 10, 2010 13:43

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.