Disulfiram

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Disulfiram
Systematic (IUPAC) name
1-(diethylthiocarbamoyldisulfanyl)- N,N-diethyl-methanethioamide
Identifiers
CAS number	97-77-8
ATC code	N07 BB01 P03 AA04
PubChem	3117
DrugBank	APRD00767
Chemical data
Formula	(C₅H₁₀NS₂)₂
Mol. weight	296.543 g/mol
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic to diethylthiocarbamate
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	C (US)
Legal status
Routes	Oral

Disulfiram 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 and Antabus 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.

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. 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, nausea, and vomiting.

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.

The drug's action was discovered by accident in the 1948 by the researchers Erik Jacobsen and Jens Hald 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.

From a practical standpoint, disulfiram is not a "cure" for alcoholism, since it is easier for an alcoholic to stop taking disulfiram than alcohol; if the treatment is not supervised, an alcoholic may abandon the treatment — and even when disulfiram therapy is strictly enforced, the negative effects are rarely enough to break the drinking patterns of a chronic alcoholic. In some extreme cases, patients with subcutaneous disulfiram tablet implants have been known to cut or dig out the tablet to avoid its effects. For these reasons, disulfiram is usually only indicated for select patients who wish to remain in an enforced state of sobriety during other forms of treatment, such as support groups and psychotherapy.

1 Similarly acting substances
2 Dangerous drug interactions
3 Organic chemistry
4 See also
5 External links

[edit] 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.

[edit] 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 into norepinephrine. 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.