is a drug
used to support the treatment of chronic alcoholism
by producing an acute sensitivity to alcohol
. Trade names for disulfiram in different countries are Antabuse
manufactured by Odyssey Pharmaceuticals
. Disulfiram is also being studied as a treatment for cocaine
dependence, as it prevents the breakdown of dopamine
(a neurotransmitter whose release is stimulated by cocaine); the excess dopamine results in increased anxiety, higher blood pressure, restlessness and other unpleasant symptoms. Several studies have reported that it has anti-protozoal
activity as well.
Research for possible disulfiram use in cancer therapy has been anounced.
Interaction with alcohol
Under normal metabolism
, alcohol is broken down in the liver
by the enzyme alcohol dehydrogenase
, 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. After alcohol intake under the influence of disulfiram, the concentration of acetaldehyde in the blood may be 5 to 10 times higher than that found during metabolism of the same amount of alcohol alone. As acetaldehyde is one of the major causes of the symptoms of a "hangover
" this produces immediate and severe negative reaction to alcohol intake. Some 5-10 minutes after alcohol intake, the patient may experience the effects of a severe hangover
for a period of 30 minutes up to several hours. Symptoms include flushing
of the skin, accelerated heart rate, shortness of breath
, throbbing headache, visual disturbance, mental confusion, postural fainting
and circulatory collapse
Disulfiram should not be taken if alcohol has been consumed in the last 12 hours. There is no tolerance to disulfiram: the longer it is taken, the stronger its effects. As disulfiram is absorbed slowly through the digestive tract and eliminated slowly by the body the effects may last for up to 2 weeks after the initial intake; consequently, medical ethics dictate that patients must be fully informed about the disulfiram-alcohol reaction. Possible side effects while taking Disulfiram are numbness or tingling of the lower legs and shortness of breath.
Disulfiram is supplied in 200 mg, 250 mg and 500 mg tablets. The usual initial dose is 500 mg for 1 to 2 weeks, followed by a maintenance dose of 250 mg (range 125 mg - 500 mg) per day. The total daily dosage should not exceed 500 mg.
History and Antiprotozoal use
The drug's action was discovered by accident in 1948
by the researchers Erik Jacobsen, Jens Hald, and Keneth Ferguson at the Danish
drug company Medicinalco
. The substance was intended to provide a remedy for parasitic infestations; however, workers testing the substance on themselves reported severe symptoms after alcohol consumption.
A study reported that it may be potentially useful in the treatment of Giardia infection. Another study found that it had activity against Trichomonas vaginalis which was resistant to the most common treatment, Metronidazole.
Similarly acting substances
Coprine (N5-1-hydroxycyclopropyl-L-glutamine) which metabolises to 1-aminocyclopropanol, a closely-related chemical having the same metabolic effects, occurs naturally in several edible mushroom
species, such as the Common Ink Cap
Temposil, or citrated calcium carbamide, has the same function as disulfiram, but is weaker and safer.
Griseofulvin, an oral anti-fungal drug.
Dangerous drug interactions
Disulfiram should not be administered to patients who take certain stimulant drugs and antidepressants. Disulfiram has been found to inhibit the enzyme dopamine-beta-hydroxylase
, blocking the metabolism of dopamine
. Combined with the dopamine
agonist and/or reuptake
effect of stimulants
, this can cause a dramatic rise in synaptic dopamine levels, resulting in sleeplessness, paranoia, and, in extreme cases, stimulant psychosis
Drugs that are known to interfere with the dopamine / norepinephrine system include, but are not limited to:
- Bupropion (Wellbutrin IR/SR/XL, Amfebutamone)
- Amphetamines (Adderall, Dexedrine, etc.)
- Methylphenidate (Ritalin, Concerta, Focalin, etc.)
- Cocaine (Occasionally used in dental procedures, and a known substance of abuse.)
The metabolism of other drugs may be inhibited by disulfiram, increasing their potential for toxic effects. Drugs known to have adverse effects when used concurrently with disulfiram include amitriptyline, isoniazid, and metronidazole (all with acute changes in mental state), phenytoin, some benzodiazepines, morphine, pethidine, and barbiturates.
Disulfiram and cancer treatment
A patient with metastatic ocular melanoma was successfully treated by disulfiram with zinc gluconate
This can be explained as disulfiram creating complexes with metals (dithiocarbamate
complexes) is proteasome inhibitor
and can represent a new approach to proteasome
Clinical trials are recommended.
Disulfiram is an example of a thiuram disulfide
, that is the oxidized derivative of diethyldithiocarbamate