Disulfiram is a
medication
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...
used to support the treatment of chronic
alcoholism
Alcoholism is, broadly, any drinking of alcohol (drug), alcohol that results in significant Mental health, mental or physical health problems. Because there is disagreement on the definition of the word ''alcoholism'', it is not a recognize ...
by producing an acute sensitivity to
ethanol
Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...
(drinking alcohol). Disulfiram works by
inhibiting the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
acetaldehyde dehydrogenase
Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows:
Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NA ...
, causing many of the effects of a
hangover
A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical sympto ...
to be felt immediately following alcohol consumption. Disulfiram plus alcohol, even small amounts, produces flushing, throbbing in the head and neck, a throbbing headache, respiratory difficulty, nausea, copious vomiting, sweating, thirst, chest pain, palpitation,
dyspnea
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathing, breathe well enough. The American Thoracic Society defines it as "a subjective experience of brea ...
,
hyperventilation
Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blood. ...
,
fast heart rate
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
,
low blood pressure
Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...
,
fainting
Syncope, commonly known as fainting, or passing out, is a loss of consciousness and muscle strength characterized by a fast onset, short duration, and spontaneous recovery. It is caused by a decrease in blood flow to the brain, typically from ...
, marked uneasiness, weakness,
vertigo
Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
, blurred vision, and confusion. In severe reactions there may be respiratory depression, cardiovascular collapse,
abnormal heart rhythms,
heart attack
A myocardial infarction (MI), commonly known as a heart attack, occurs when blood flow decreases or stops to the coronary artery of the heart, causing damage to the heart muscle. The most common symptom is chest pain or discomfort which may tr ...
, acute
congestive heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, unconsciousness, convulsions, and death.
In the body, alcohol is converted to
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
, which is then broken down by acetaldehyde dehydrogenase. When the dehydrogenase enzyme is inhibited, acetaldehyde builds up, causing unpleasant side effects. Disulfiram should be used in conjunction with counseling and support.
Medical uses
Disulfiram is used as a second-line treatment, behind
acamprosate
Acamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol use disorder. For label updates seFDA index page for NDA 021431/ref>
Acamprosate is thought to stabilize chemical signaling in the brai ...
and
naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
, for
alcohol dependence
Alcohol dependence is a previous (DSM-IV and ICD-10) psychiatric diagnosis in which an individual is physically or psychologically dependent upon alcohol (also chemically known as ethanol).
In 2013, it was reclassified as alcohol use disorde ...
.
Under normal
metabolism
Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...
, alcohol is broken down in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
by the
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...
alcohol dehydrogenase
Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to N ...
to
acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
, which is then converted by the enzyme
acetaldehyde dehydrogenase
Acetaldehyde dehydrogenases () are dehydrogenase enzymes which catalyze the conversion of acetaldehyde into acetic acid. The oxidation of acetaldehyde to acetate can be summarized as follows:
Acetaldehyde + NAD+ + Coenzyme A ↔ Acetyl-CoA + NA ...
to a harmless
acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
derivative (
acetyl coenzyme A
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
). Disulfiram blocks this reaction at the intermediate stage by blocking acetaldehyde dehydrogenase. After alcohol intake under the influence of disulfiram, the concentration of acetaldehyde in the blood may be five 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
A hangover is the experience of various unpleasant physiological and psychological effects usually following the consumption of alcohol, such as wine, beer, and liquor. Hangovers can last for several hours or for more than 24 hours. Typical sympto ...
", this produces immediate and severe negative reaction to alcohol intake. About 5 to 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
Flushing may refer to:
Places
* Flushing, Cornwall, a village in the United Kingdom
* Flushing, Queens, New York City
** Flushing Bay, a bay off the north shore of Queens
** Flushing Chinatown (法拉盛華埠), a community in Queens
** Flushing ...
of the skin, accelerated heart rate,
shortness of breath
Shortness of breath (SOB), also medically known as dyspnea (in AmE) or dyspnoea (in BrE), is an uncomfortable feeling of not being able to breathe well enough. The American Thoracic Society defines it as "a subjective experience of breathing disc ...
,
nausea
Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...
,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the Human nose, nose.
Vomiting can be the result of ailments like Food-poisoning, foo ...
, throbbing headache, visual disturbance, mental confusion,
postural syncope, and
circulatory collapse
Shock is the state of insufficient blood flow to the tissues of the body as a result of problems with the circulatory system. Initial symptoms of shock may include weakness, fast heart rate, fast breathing, sweating, anxiety, and increased thi ...
.
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 two weeks after the initial intake; consequently, ]medical ethics
Medical ethics is an applied branch of ethics which analyzes the practice of clinical medicine and related scientific research. Medical ethics is based on a set of values that professionals can refer to in the case of any confusion or conflict. T ...
dictate that patients must be fully informed about the disulfiram-alcohol reaction.
Disulfiram does not reduce alcohol cravings, so a major problem associated with this drug is extremely poor compliance. Methods to improve compliance include subdermal implants, which release the drug continuously over a period of up to 12 weeks, and supervised administration practices, for example, having the drug regularly administered by one's spouse.
Although disulfiram remained the most common pharmaceutical treatment of alcohol abuse
Alcohol abuse encompasses a spectrum of unhealthy alcohol drinking behaviors, ranging from binge drinking to alcohol dependence, in extreme cases resulting in health problems for individuals and large scale social problems such as alcohol-relat ...
until the end of the 20th century, today it is often replaced or accompanied with newer drugs, primarily the combination of naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
and acamprosate
Acamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol use disorder. For label updates seFDA index page for NDA 021431/ref>
Acamprosate is thought to stabilize chemical signaling in the brai ...
, which directly attempt to address physiological processes in the brain associated with alcohol abuse.
Side effects
The most common side effects in the absence of alcohol are headache, and a metallic or garlic taste in the mouth, though more severe side effects may occur. Tryptophol
Tryptophol is an aromatic alcohol that induces sleep in humans. It is found in wine as a secondary product of ethanol fermentation. It was first described by Felix Ehrlich in 1912. It is also produced by the trypanosomal parasite in sleeping sic ...
, a chemical compound that induces sleep in humans, is formed in the liver after disulfiram treatment. Less common side effects include decrease in libido, liver problems, skin rash, and nerve inflammation. Liver toxicity is an uncommon but potentially serious side effect, and risk groups e.g. those with already impaired liver function should be monitored closely. That said, the rate of disulfiram-induced hepatitis are estimated to be in between 1 per 25,000 to 1 in 30,000, and rarely the primary cause for treatment cessation.
Cases of disulfiram neurotoxicity have also occurred, causing extrapyramidal and other symptoms. Disulfiram can produce neuropathy in daily doses of less than the usually recommended 500 mg. Nerve biopsies showed axonal degeneration and the neuropathy is difficult to distinguish from that associated with ethanol abuse. Disulfiram neuropathy occurs after a variable latent period (mean 5 to 6 months) and progresses steadily. Slow improvement may occur when the drug's use is stopped; often there is complete recovery eventually.
Disulfiram disrupts metabolism of several other compounds, including paracetamol
Paracetamol, also known as acetaminophen, is a medication used to treat fever and mild to moderate pain. Common brand names include Tylenol and Panadol.
At a standard dose, paracetamol only slightly decreases body temperature; it is inferior ...
(acetaminophen), theophylline
Theophylline, also known as 1,3-dimethylxanthine, is a phosphodiesterase inhibiting drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. As a member of the ...
and caffeine
Caffeine is a central nervous system (CNS) stimulant of the methylxanthine class. It is mainly used recreationally as a cognitive enhancer, increasing alertness and attentional performance. Caffeine acts by blocking binding of adenosine t ...
. However, in most cases, this disruption is mild and presents itself as a 20–40% increase in the half-life of the compound at typical dosages of disulfiram.
Similarly acting substances
In medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pract ...
, the term "disulfiram effect" refers to an adverse effect of a particular medication in causing an unpleasant hypersensitivity to alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
, similar to the effect caused by disulfiram administration.
Examples:
* Antibiotics (nitroimidazoles), e.g. metronidazole
Metronidazole, sold under the brand name Flagyl among others, is an antibiotic and antiprotozoal medication. It is used either alone or with other antibiotics to treat pelvic inflammatory disease, endocarditis, and bacterial vaginosis. It is ef ...
* First-generation sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s, e.g. tolbutamide
Tolbutamide is a first-generation potassium channel blocker, sulfonylurea oral hypoglycemic medication. This drug may be used in the management of type 2 diabetes if diet alone is not effective. Tolbutamide stimulates the secretion of insulin by ...
and chlorpropamide
Chlorpropamide is a drug in the sulfonylurea class used to treat diabetes mellitus type 2. It is a long-acting first-generation sulfonylurea.
Mechanism of action
Like other sulfonylureas, chlorpropamide acts to increase the secretion of insulin, ...
* Several cephalosporin
The cephalosporins (sg. ) are a class of β-lactam antibiotics originally derived from the fungus ''Acremonium'', which was previously known as ''Cephalosporium''.
Together with cephamycins, they constitute a subgroup of β-lactam antibiotics ...
drugs, including cefoperazone
Cefoperazone is a third-generation cephalosporin antibiotic, marketed by Pfizer under the name Cefobid. It is one of few cephalosporin antibiotics effective in treating ''Pseudomonas'' bacterial infections which are otherwise resistant to these ...
, cefamandole
Cefamandole (INN, also known as cephamandole) is a second-generation broad-spectrum cephalosporin antibiotic. The clinically used form of cefamandole is the formate ester cefamandole nafate, a prodrug which is administered parenterally. Cef ...
and cefotetan
Cefotetan is an injectable antibiotic of the cephamycin type for prophylaxis and treatment of bacterial infections. It is often grouped together with second-generation cephalosporins and has a similar antibacterial spectrum, but with additional ...
, that have a N-methylthio-tetrazole moiety
* Griseofulvin
Griseofulvin is an antifungal medication used to treat a number of types of dermatophytoses (ringworm). This includes fungal infections of the nails and scalp, as well as the skin when antifungal creams have not worked. It is taken by mouth.
C ...
, an oral antifungal drug
* Procarbazine
Procarbazine is a chemotherapy medication used for the treatment of Hodgkin's lymphoma and brain cancers. For Hodgkin's it is often used together with chlormethine, vincristine, and prednisone while for brain cancers such as glioblastoma multif ...
* Temposil
Calcium carbimide, sold as the citrate salt under the trade name Temposil, is a disulfiram-like medication. Its effects are similar to the medication disulfiram (Antabuse) in that it interferes with the normal metabolism of alcohol by preventin ...
, or citrated calcium carbimide, has the same function as disulfiram, but is weaker and safer.
* Coprine
Coprine is a mycotoxin. It was first isolated from common inkcap (''Coprinopsis atramentaria''). It occurs in mushrooms in the genera ''Coprinopsis'' When combined with alcohol, it causes "Coprinus syndrome". It inhibits the enzyme acetaldehyde ...
, which metabolizes to 1-aminocyclopropanol, a chemical having the same metabolic effects as disulfiram. It occurs naturally in the otherwise edible common ink cap mushroom (''Coprinopsis atramentaria
''Coprinopsis atramentaria'', commonly known as the common ink cap or inky cap, is an edible (although poisonous when combined with alcohol) mushroom found in Europe and North America. Previously known as ''Coprinus atramentarius'', it is th ...
''), hence its colloquial name "tippler's bane". Similar reactions have been recorded with '' Clitocybe clavipes'' and '' Suillellus luridus'', although the agent in those species is unknown.
History
The synthesis of disulfiram, originally known as tetraethylthiuram disulfide, was first reported in 1881. By around 1900, it was introduced to the industrial process of sulfur vulcanization
Sulfur vulcanization is a chemical process for converting natural rubber or related polymers into materials of varying hardness, elasticity, and mechanical durability by heating them with sulfur or sulfur-containing compounds. Sulfur forms cros ...
of rubber and became widely used. In 1937 a rubber factory doctor in the US published a paper noting that workers exposed to disulfiram had negative reactions to alcohol and could be used as a drug for alcoholism; the effects were also noticed in workers at a Swedish rubber boot factory.
In the early 1940s it had been tested as a treatment for scabies
Scabies (; also sometimes known as the seven-year itch) is a contagious skin infestation by the mite ''Sarcoptes scabiei''. The most common symptoms are severe itchiness and a pimple-like rash. Occasionally, tiny burrows may appear on the skin ...
, a parasitic skin infection, as well as intestinal worms.[
Around that time, during the ]German occupation of Denmark
At the outset of World War II in September 1939, Denmark declared itself neutral. For most of the war, the country was a protectorate and then an occupied territory of Germany. The decision to occupy Denmark was taken in Berlin on 17 December ...
, Erik Jacobsen and Jens Hald at the Danish drug company Medicinalco picked up on that research and began exploring the use of disulfiram to treat intestinal parasites. The company had a group of enthusiastic self-experimenters that called itself the "Death Battalion", and in the course of testing the drug on themselves, accidentally discovered that drinking alcohol while the drug was still in their bodies made them mildly sick.
They made that discovery in 1945, and did nothing with it until two years later, when Jacobsen gave an impromptu talk and mentioned that work, which was discussed afterwards in newspapers at the time, leading them to further explore the use of the drug for that purpose.[ That work included small clinical trials with Oluf Martensen-Larsen, a doctor who worked with alcoholics.][ They published their work starting in 1948.][
The chemists at Medicinalco discovered a new ]form
Form is the shape, visual appearance, or configuration of an object. In a wider sense, the form is the way something happens.
Form also refers to:
*Form (document), a document (printed or electronic) with spaces in which to write or enter data
...
of disulfiram while trying to purify a batch that had been contaminated with copper. This form turned out to have better pharmacological properties, and the company patented it and used that form for the product that was introduced as Antabus (later anglicized to Antabuse).[
This work led to renewed study of the human metabolism of ethanol. It was already known that ethanol was mostly metabolized in the liver, with it being converted first to acetaldehyde and then acetaldehyde to acetic acid and carbon dioxide, but the enzymes involved were not known. By 1950 the work led to the knowledge that ethanol is oxidized to ]acetaldehyde
Acetaldehyde (IUPAC systematic name ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is a colorless liquid or gas, boiling near room temperature. It is one of the mos ...
by alcohol dehydrogenase
Alcohol dehydrogenases (ADH) () are a group of dehydrogenase enzymes that occur in many organisms and facilitate the interconversion between alcohols and aldehydes or ketones with the reduction of nicotinamide adenine dinucleotide (NAD+) to N ...
and acetaldehyde is oxidized to acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main component ...
by aldehyde dehydrogenase
Aldehyde dehydrogenases () are a group of enzymes that catalyse the oxidation of aldehydes. They convert aldehydes (R–C(=O)) to carboxylic acids (R–C(=O)). The oxygen comes from a water molecule. To date, nineteen ALDH genes have b ...
(ALDH), and that disulfiram works by inhibiting ALDH, leading to a buildup of acetaldehyde, which is what causes the negative effects in the body.[
The drug was first marketed in Denmark and as of 2008, Denmark is the country where it is most widely prescribed. It was approved by the FDA in 1951.][ The FDA later approved other drugs for treatment of alcoholism, namely ]naltrexone
Naltrexone, sold under the brand name Revia among others, is a medication primarily used to manage alcohol or opioid use disorder by reducing cravings and feelings of euphoria associated with substance use disorder. It has also been found t ...
in 1994 and acamprosate
Acamprosate, sold under the brand name Campral, is a medication used along with counselling to treat alcohol use disorder. For label updates seFDA index page for NDA 021431/ref>
Acamprosate is thought to stabilize chemical signaling in the brai ...
in 2004.[
]
Society and culture
Though the Occupational Safety and Health Administration
The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...
(OSHA) in the US has not set a permissible exposure limit
The permissible exposure limit (PEL or OSHA PEL) is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent such as high level noise. Permissible exposure limits are established by the Occupational S ...
(PEL) for disulfiram in the workplace, the National Institute for Occupational Safety and Health
The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...
has set a recommended exposure limit
A recommended exposure limit (REL) is an occupational exposure limit that has been recommended by the United States National Institute for Occupational Safety and Health. The REL is a level that NIOSH believes would be protective of worker safety ...
(REL) of 2 mg/m3 and recommended that workers avoid concurrent exposure to ethylene dibromide
1,2-Dibromoethane, also known as ethylene dibromide (EDB), is an organobromine compound with the chemical formula . Although trace amounts occur naturally in the ocean, where it is formed probably by algae and kelp, it is mainly synthetic. It is a ...
.
Research
Disulfiram has been studied as a possible treatment for cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...
, parasitic infections, anxiety disorder, and latent HIV infection
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ma ...
.
Disulfiram has shown reversing of retinitis pigmentosa
Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...
in rats.
Cancer
When disulfiram creates complexes with metals (dithiocarbamate
In organic chemistry, a dithiocarbamate is a functional group with the general formula and structure . It is the analog of a carbamate in which both oxygen atoms are replaced by sulfur atoms (when only 1 oxygen is replaced the result is thioca ...
complexes), it is a proteasome inhibitor
Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. They are being studied in the treatment of cancer; and three are approved for use in treating multiple myeloma.
Mechanism
Multipl ...
and as of 2016 it had been studied in ''in vitro'' experiments, model animals, and small clinical trials as a possible treatment for liver metastasis, metastatic melanoma, glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
, non-small cell lung cancer, and prostate cancer.[ Various clinical trials of copper depletion agents have been carried out.
]
Parasitic infections
In the body, disulfiram is rapidly metabolized to diethyldithiocarbamate (ditiocarb), which binds to metal ions such as zinc or copper to form zinc or copper diethyldithiocarbamate (zinc or copper ditiocarb). The zinc diethyldithiocarbamate (zinc-ditiocarb) metabolite of disulfiram is extremely potent against the diarrhea and liver abscess-causing parasite ''Entamoeba histolytica
''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...
'' and might be active against other deadly parasites.
HIV
Disulfiram has also been identified by systematic high-throughput screening
High-throughput screening (HTS) is a method for scientific experimentation especially used in drug discovery and relevant to the fields of biology, materials science and chemistry. Using robotics, data processing/control software, liquid handlin ...
as a potential HIV
The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...
latency reversing agent (LRA). Reactivation of latent HIV infection in patients is part of an investigational strategy known as "shock and kill" which may be able to reduce or eliminate the HIV reservoir.[ Recent phase II dose-escalation studies in patients with HIV who are controlled on ]antiretroviral therapy
The management of HIV/AIDS normally includes the use of multiple Antiviral drug, antiretroviral drugs as a strategy to control HIV/AIDS, HIV infection. There are several classes of antiretroviral agents that act on different stages of the HIV life- ...
have observed an increase in cell-associated unspliced HIV RNA with increasing exposure to disulfiram and its metabolites. Disulfiram is also being investigated in combination with vorinostat
Vorinostat (rINN) also known as Suberoylanilide hydroxamic acid ( suberoyl+anilide+hydroxamic acid abbreviated as SAHA) is a member of a larger class of compounds that inhibit histone deacetylases (HDAC). Histone deacetylase inhibitors (HDI) ha ...
, another investigational latency reversing agent, to treat HIV.
COVID-19
Disulfiram has been shown to inhibit the papain-like proteases of MERS-CoV
''Middle East respiratory syndrome–related coronavirus'' (''MERS-CoV''), or EMC/2012 ( HCoV-EMC/2012), is the virus that causes Middle East respiratory syndrome (MERS). It is a species of coronavirus which infects humans, bats, and camels. The ...
and SARS-CoV
Severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; or Severe acute respiratory syndrome coronavirus, SARS-CoV) is a strain of coronavirus that causes severe acute respiratory syndrome (SARS), the respiratory illness responsible for t ...
. It has been examined in a small inconclusive retrospective observational study for its effects on COVID-19
Coronavirus disease 2019 (COVID-19) is a contagious disease caused by a virus, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The first known case was COVID-19 pandemic in Hubei, identified in Wuhan, China, in December ...
symptoms and is currently in Phase 2 clinical trials.
References
External links
*
*
CDC - NIOSH Pocket Guide to Chemical Hazards
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