Top Gene Interactions
- Metabolism: Disulfiram is completely absorbed from the human GI tract. However, a period of 12 hr is required for its full action, perhaps because, being highly sol in lipid, it is initially localized in fat. It is slowly metabolized in the liver to diethyldithiocarbamate, diethylamine, and carbon disulfide. Six hr after oral administration of the drug, one third of plasma disulfiram is in the form of diethyldithiocarbamate. Elimination is relatively slow, and about 1/5 still remains in body at end of a week. The greater part of the absorbed drug is excreted in the urine as the sulfate, partly free and partly esterified (A620, A622).
- Uses/Sources: For the treatment and management of chronic alcoholism (A308).
- Health Effects: Occasionally implicated in producing psychosis, optic neuritis, and encephalopathy. Hematologic, neuromuscular, and gastrointestinal toxicity and hepatotoxicity may occur 10 days to 12 months after therapy is begun (T36).
- Symptoms: Symptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.
- Route of Exposure: Inhalation (MSDS, A308); ingestion (MSDS, A308); dermal (MSDS, A308) ; eye contact (MSDS, A308) Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).
- Carcinogenicity: 3, not classifiable as to its carcinogenicity to humans. (L135)
- Toxicity: LD50: 8.6g/kg (oral, rat).
Mechanism of Action
|Target Name||Mechanism of Action||References|
Aldehyde dehydrogenase family 1 member A3
Aldehyde dehydrogenase, dimeric NADP-preferring
Aldehyde dehydrogenase family 3 member B1
Aldehyde dehydrogenase family 3 member B2
Aldehyde dehydrogenase X, mitochondrial
Aldehyde dehydrogenase family 16 member A1
Aldehyde dehydrogenase family 8 member A1
|Under normal metabolism, alcohol is broken down in the liver by the enzyme alcohol dehydrogenase to acetaldehyde, which is then converted by the enzyme acetaldehyde dehydrogenase to the harmless acetic acid. Disulfiram blocks this reaction at the intermediate stage by blocking the enzyme acetaldehyde dehydrogenase. (L1015)||
Cellular tumor antigen p53
Peroxisome proliferator-activated receptor gamma
Fatty-acid amide hydrolase 1
5-hydroxytryptamine receptor 7
D(1A) dopamine receptor
5-hydroxytryptamine receptor 6
Cytochrome P450 2C9
Cytochrome P450 2C19
Type-1 angiotensin II receptor
Aldehyde dehydrogenase, mitochondrial
|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.||