Drug/Small Molecule:

disulfiram

Overview

Generic Names:	Disulfuram; Disulphuram; Dupon 4472; Dupont Fungicide 4472; TATD; TETD; TTD; Tetraethylthioperoxydicarbonic Diamide; Tetraethylthiram Disulfide; Tetraethylthiram Disulphide; Tetraethylthiuram; Tetraethylthiuram Disulfide; Tetraethylthiuram Disulphide; Tetraethylthiuram Sulfide; Tetraethylthiuran Disulfide; Usaf B-33
IUPAC Name:	diethylcarbamothioylsulfanyl diethylaminomethanedithioate
Trade 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; TTS; TTS X; Tenurid; Tenutex; Tetidis; Tetradin; Tetradine; Tetraetil; Teturam; Teturamin; Thiocid; Thiophos; Thioscabin; Thireranide; Tillram; Tiuram
PharmGKB Accession Id:	PA449376

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]

Indication

For the treatment and management of chronic alcoholism

ATC Therapeutic Categories

• N07BB:Drugs used in alcohol dependence
• P03AA:Sulfur containing products

Pharmacology and Interactions

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.

Pharmacology

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.

Food Interactions

Avoid alcohol for up to 14 days after treatment has been stopped. Take without regard to meals.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic.

Absorption

Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).

Toxicity

LD₅₀=8.6g/kg (orally in rats). Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.

Chemical Properties

Chemical Formula:

C₁₀H₂₀N₂S₄

SMILES Code:

CCN(CC)C(=S)SSC(=S)N(CC)CC

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

296.539 / 296.0509

Curated Information

The following genes are in curated knowledge about this drug.

	Gene	Relationship	Evidence
	ABCB1	FA	Publications
	DBH	FA	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

• TSPO
• ALDH2

PharmGKB Curated Pathways

• Sympathetic Nerve Pathway (Neuroeffector Junction)

Curated Information

The following drugs are in curated knowledge about this drug.

	Drug	Relationship	Evidence
	warfarin		Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Curated Information

The following diseases are in curated knowledge about this drug.

	Disease	Relationship	Evidence
	Alcoholism	FA	Publications
	Cocaine-Related Disorders	FA	Publications
	Hypotension	FA	Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

1. The Connectivity Map: using gene-expression signatures to connect small molecules, genes, and disease

LinkOuts

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.