Dimercaprol

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Dimercaprol
Dimercaprol.svg
Dimercaprol-3D-balls.png
Skeletal formula and ball and stick model of dimercaprol
Clinical data
Trade names BAL in Oil
Other names2,3-Dimercaptopropanol
British Anti-Lewisite
2,3-Dithiopropanol
2,3-Dimercaptopropan-1-ol
British antilewisite
AHFS/Drugs.com Monograph
License data
Routes of
administration
intramuscular
ATC code
Legal status
Legal status
Pharmacokinetic data
Excretion Urine [1]
Identifiers
  • 2,3-Bis(sulfanyl)propan-1-ol [2]
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.000.394 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C3H8OS2
Molar mass 124.22 g·mol−1
3D model (JSmol)
Density 1.239 g/cm3
Boiling point 393 °C (739 °F) at 2.0 kPa
  • OCC(S)CS
  • InChI=1S/C3H8OS2/c4-1-3(6)2-5/h3-6H,1-2H2 Yes check.svgY
  • Key:WQABCVAJNWAXTE-UHFFFAOYSA-N

Dimercaprol, also called British anti-Lewisite (BAL), is a medication used to treat acute poisoning by arsenic, mercury, gold, and lead. [3] It may also be used for antimony, thallium, or bismuth poisoning, although the evidence for those uses is not very strong. [3] [4] It is given by injection into a muscle. [3]

Contents

Common side effects include high blood pressure, pain at the site of the injection, vomiting, and fever. [3] It is not recommended for people with peanut allergies as it is typically formulated as a suspension in peanut oil. [3] It is unclear if use in pregnancy is safe for the baby. [3] Dimercaprol is a chelator and works by binding with heavy metals. [3] It has a very pungent odor.

Dimercaprol was first made during World War II. [5] It is on the World Health Organization's List of Essential Medicines. [6]

Medical uses

Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, [7] and it is an essential drug. [6] It is also used as an antidote to the chemical weapon Lewisite. Nonetheless, because it can have serious adverse effects, researchers have also pursued development of less toxic analogues, [7] such as succimer.

Wilson's disease is a genetic disorder in which copper builds up inside the liver and other tissues. Dimercaprol is a copper chelating agent that has been approved by the FDA to treat Wilson's disease. [8]

Dimercaprol also shows effectiveness against snakebite by potently antagonizing the activity of Zn 2+-dependent snake venom metalloproteinases in vitro . [9]

Mechanism of action

Arsenic and some other heavy metals act by chelating with adjacent thiol residues on metabolic enzymes, creating a chelate complex that inhibits the affected enzyme's activity. [10] Dimercaprol competes with the thiol groups for binding the metal ion, which is then excreted in the urine.[ citation needed ]

Dimercaprol is itself toxic, with a narrow therapeutic range and a tendency to concentrate arsenic in some organs. Other drawbacks include the need to administer it by painful intramuscular injection [11] Serious side effects include nephrotoxicity and hypertension.

Dimercaprol has been found to form stable chelates in vivo with many other metals including inorganic mercury, antimony, bismuth, cadmium, chromium, cobalt, gold, and nickel. However, it is not necessarily the treatment of choice for toxicity to these metals. Dimercaprol has been used as an adjunct in the treatment of the acute encephalopathy of lead toxicity. It is a potentially toxic drug, and its use may be accompanied by multiple side effects. Although treatment with dimercaprol will increase the excretion of cadmium, there is a concomitant increase in renal cadmium concentration, so that its use in case of cadmium toxicity is to be avoided. It does, however, remove inorganic mercury from the kidneys; but is not useful in the treatment of alkylmercury or phenylmercury toxicity. Dimercaprol also enhances the toxicity of selenium and tellurium, so it is not to be used to remove these elements from the body.[ citation needed ]

History

The original name of dimercaprol reflects its origins as a compound secretly developed by British biochemists at Oxford University in the beginning of the World War II, with the first synthesis in July 1940 [12] [13] as an antidote for lewisite, a now-obsolete arsenic-based chemical warfare agent. [12]

See also

Related Research Articles

<span class="mw-page-title-main">Toxic heavy metal</span> Category of substances

A toxic heavy metal is any relatively dense metal or metalloid that is noted for its potential toxicity, especially in environmental contexts. The term has particular application to cadmium, mercury and lead, all of which appear in the World Health Organization's list of 10 chemicals of major public concern. Other examples include manganese, chromium, cobalt, nickel, copper, zinc, silver, antimony and thallium.

<span class="mw-page-title-main">Arsenic poisoning</span> Illness from ingesting arsenic

Arsenic poisoning is a medical condition that occurs due to elevated levels of arsenic in the body. If arsenic poisoning occurs over a brief period of time, symptoms may include vomiting, abdominal pain, encephalopathy, and watery diarrhea that contains blood. Long-term exposure can result in thickening of the skin, darker skin, abdominal pain, diarrhea, heart disease, numbness, and cancer.

Chelation is a type of bonding of ions and the molecules to metal ions. It involves the formation or presence of two or more separate coordinate bonds between a polydentate ligand and a single central metal atom. These ligands are called chelants, chelators, chelating agents, or sequestering agents. They are usually organic compounds, but this is not a necessity.

<span class="mw-page-title-main">Lewisite</span> Arsenic compound and chemical weapon

Lewisite (L) (A-243) is an organoarsenic compound. It was once manufactured in the U.S., Japan, Germany and the Soviet Union for use as a chemical weapon, acting as a vesicant and lung irritant. Although the substance is colorless and odorless in its pure form, impure samples of lewisite are a yellow, brown, violet-black, green, or amber oily liquid with a distinctive odor that has been described as similar to geraniums.

<span class="mw-page-title-main">Mercury poisoning</span> Poisoning caused by mercury chemicals

Mercury poisoning is a type of metal poisoning due to exposure to mercury. Symptoms depend upon the type, dose, method, and duration of exposure. They may include muscle weakness, poor coordination, numbness in the hands and feet, skin rashes, anxiety, memory problems, trouble speaking, trouble hearing, or trouble seeing. High-level exposure to methylmercury is known as Minamata disease. Methylmercury exposure in children may result in acrodynia in which the skin becomes pink and peels. Long-term complications may include kidney problems and decreased intelligence. The effects of long-term low-dose exposure to methylmercury are unclear.

<span class="mw-page-title-main">Chelation therapy</span> Medical procedure to remove heavy metals from the body

Chelation therapy is a medical procedure that involves the administration of chelating agents to remove heavy metals from the body. Chelation therapy has a long history of use in clinical toxicology and remains in use for some very specific medical treatments, although it is administered under very careful medical supervision due to various inherent risks, including the mobilization of mercury and other metals through the brain and other parts of the body by the use of weak chelating agents that unbind with metals before elimination, exacerbating existing damage. To avoid mobilization, some practitioners of chelation use strong chelators, such as selenium, taken at low doses over a long period of time.

Cadmium is a naturally occurring toxic metal with common exposure in industrial workplaces, plant soils, and from smoking. Due to its low permissible exposure in humans, overexposure may occur even in situations where only trace quantities of cadmium are found. Cadmium is used extensively in electroplating, although the nature of the operation does not generally lead to overexposure. Cadmium is also found in some industrial paints and may represent a hazard when sprayed. Operations involving removal of cadmium paints by scraping or blasting may pose a significant hazard. The primary use of cadmium is in the manufacturing of NiCd rechargeable batteries. The primary source for cadmium is as a byproduct of refining zinc metal. Exposures to cadmium are addressed in specific standards for the general industry, shipyard employment, the construction industry, and the agricultural industry.

<span class="mw-page-title-main">Succimer</span> Medication used to treat lead, mercury, and arsenic poisoning

Succimer, sold under the brand name Chemet among others, is a medication used to treat lead, mercury, and arsenic poisoning. When radiolabeled with technetium-99m, it is used in many types of diagnostic testing. A full course of Succimer lasts for 19 days of oral administration. A second course should be given when more than two weeks pass after the first course.

<span class="mw-page-title-main">Penicillamine</span> Chemical compound

Penicillamine, sold under the brand name of Cuprimine among others, is a medication primarily used for the treatment of Wilson's disease. It is also used for people with kidney stones who have high urine cystine levels, rheumatoid arthritis, and various heavy metal poisonings. It is taken by mouth.

Deferoxamine (DFOA), also known as desferrioxamine and sold under the brand name Desferal, is a medication that binds iron and aluminium. It is specifically used in iron overdose, hemochromatosis either due to multiple blood transfusions or an underlying genetic condition, and aluminium toxicity in people on dialysis. It is used by injection into a muscle, vein, or under the skin.

<span class="mw-page-title-main">2,3-Dimercapto-1-propanesulfonic acid</span> Chemical compound

2,3-Dimercapto-1-propanesulfonic acid and its sodium salt are chelating agents that form complexes with various heavy metals. They are related to dimercaprol, which is another chelating agent.

<span class="mw-page-title-main">Metal toxicity</span> Harmful effects of certain metals

Metal toxicity or metal poisoning is the toxic effect of certain metals in certain forms and doses on life. Some metals are toxic when they form poisonous soluble compounds. Certain metals have no biological role, i.e. are not essential minerals, or are toxic when in a certain form. In the case of lead, any measurable amount may have negative health effects. It is often thought that only heavy metals can be toxic, but lighter metals such as beryllium and lithium may also be in certain circumstances. Not all heavy metals are particularly toxic, and some are essential, such as iron. The definition may also include trace elements when abnormally high doses may be toxic. An option for treatment of metal poisoning may be chelation therapy, a technique involving the administration of chelation agents to remove metals from the body.

BDTH<sub>2</sub> Chemical compound

BDTH2 (also called BDET and BDETH2; trade names B9, MetX, and OSR#1) is an organosulfur compound that is used as a chelation agent. It is a colourless solid. The molecule consists of two thiol groups and linked via a pair of amide groups.

Animal lead poisoning is a veterinary condition and pathology caused by increased levels of the heavy metal lead in an animal's body.

<span class="mw-page-title-main">Dithiol</span> Organosulfur compound with two –SH groups

In organic chemistry, a dithiol is a type of organosulfur compound with two thiol functional groups. Their properties are generally similar to those of monothiols in terms of solubility, odor, and volatility. They can be classified according to the relative location of the two thiol groups on the organic backbone.

Arsenic biochemistry refers to biochemical processes that can use arsenic or its compounds, such as arsenate. Arsenic is a moderately abundant element in Earth's crust, and although many arsenic compounds are often considered highly toxic to most life, a wide variety of organoarsenic compounds are produced biologically and various organic and inorganic arsenic compounds are metabolized by numerous organisms. This pattern is general for other related elements, including selenium, which can exhibit both beneficial and deleterious effects. Arsenic biochemistry has become topical since many toxic arsenic compounds are found in some aquifers, potentially affecting many millions of people via biochemical processes.

<span class="mw-page-title-main">Jeffrey Brent</span> Medical toxicologist

Jeffrey A. Brent is a medical toxicologist who is a distinguished clinical professor of medicine and emergency medicine at the University of Colorado, School of Medicine. In addition, he is a professor at the Department of Environmental and Occupational Health at the Colorado School of Public Health. He is also the past president of the American Academy of Clinical Toxicology, was editor in chief of the journal Toxicological Reviews, and was a member of the board of directors of the American College of Medical Toxicology. Previously, most of Brent's research focused on the use of fomepizole as a treatment for both methanol and ethylene glycol poisoning, and he led a trial of this drug which resulted in the FDA approving it in December 1997. Currently, Brent serves as Director of the Toxicology Investigators Consortium, an NIH and FDA supported multi center research and surveillance group. Brent is also a senior editor of "Critical Care Toxicology: Diagnosis and Management of the Critically Poisoned Patient," originally published in 2005, and now in its second edition, which was published in 2017.

<span class="mw-page-title-main">Sodium calcium edetate</span> Chemical compound

Sodium calcium edetate, also known as edetate calcium disodium among other names, is a medication primarily used to treat lead poisoning, including both short-term and long-term lead poisoning. Sodium calcium edetate came into medical use in the United States in 1953.

<span class="mw-page-title-main">Lewisite 2</span> Chemical compound

Lewisite 2(L-2) is an organoarsenic chemical weapon with the formula AsCl(CH=CHCl)2. It is similar to lewisite 1 and lewisite 3 and was first synthesized in 1904 by Julius Arthur Nieuwland. It is usually found as a mixture of 2-chlorovinylarsonous dichloride (lewisite 1) as well as bis(2-chloroethenyl) arsinous chloride (lewisite 2) and tris(2-chlorovinyl)arsine (lewisite 3). Pure lewisite 1 is an oily, colorless liquid, however, the impure mixture can appear amber to black with an odor distinct to geraniums.

<span class="mw-page-title-main">Lewisite 3</span> Chemical compound

Lewisite 3(L-3) is an organoarsenic chemical weapon like lewisite 1 and lewisite 2 first synthesized in 1904 by Julius Arthur Nieuwland. It is usually found as a mixture of 2-chlorovinylarsonous dichloride as well as bis(2-chloroethenyl) arsinous chloride and tris(2-chlorovinyl)arsine. Pure lewisite 1 is an oily, colorless liquid, however, the impure mixture can appear amber to black with an odor distinct to geraniums.

References

  1. Poisoning in Children. Jaypee Brothers Publishers. 2013. p. 70. ISBN   978-93-5025-773-9.
  2. Nomenclature of Organic Chemistry : IUPAC Recommendations and Preferred Names 2013 (Blue Book). Cambridge: The Royal Society of Chemistry. 2014. p. 697. doi:10.1039/9781849733069-FP001. ISBN   978-0-85404-182-4. The prefixes 'mercapto' (–SH), and 'hydroseleno' or selenyl (–SeH), etc. are no longer recommended.
  3. 1 2 3 4 5 6 7 "Dimercaprol". The American Society of Health-System Pharmacists. Archived from the original on 21 December 2016. Retrieved 8 December 2016.
  4. World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. p. 62. hdl: 10665/44053 . ISBN   978-92-4-154765-9.
  5. Greenwood D (2008). "Antiprotozoal Agents". Antimicrobial Drugs: Chronicle of a Twentieth Century Medical Triumph. OUP Oxford. p. 281. ISBN   978-0-19-953484-5. Archived from the original on 2016-12-20.
  6. 1 2 World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl: 10665/325771 . WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  7. 1 2 Flora SJ, Pachauri V (July 2010). "Chelation in metal intoxication". International Journal of Environmental Research and Public Health. 7 (7): 2745–2788. doi: 10.3390/ijerph7072745 . PMC   2922724 . PMID   20717537.
  8. Leggio L, Addolorato G, Abenavoli L, Gasbarrini G (2005). "Wilson's disease: clinical, genetic and pharmacological findings". International Journal of Immunopathology and Pharmacology. 18 (1): 7–14. doi:10.1177/039463200501800102. PMID   15698506. S2CID   26059921.
  9. Albulescu LO, Hale MS, Ainsworth S, Alsolaiss J, Crittenden E, Calvete JJ, et al. (May 2020). "Preclinical validation of a repurposed metal chelator as an early-intervention therapeutic for hemotoxic snakebite". Science Translational Medicine. 12 (542). doi:10.1126/scitranslmed.aay8314. PMC   7116364 . PMID   32376771.
  10. Goldman M, Dacre JC (1989). "Lewisite: Its Chemistry, Toxicology, and Biological Effects". Reviews of Environmental Contamination and Toxicology. Vol. 110. pp. 75–115. doi:10.1007/978-1-4684-7092-5_2. ISBN   978-1-4684-7094-9. PMID   2692088.
  11. Mückter H, Liebl B, Reichl FX, Hunder G, Walther U, Fichtl B (August 1997). "Are we ready to replace dimercaprol (BAL) as an arsenic antidote?". Human & Experimental Toxicology. 16 (8): 460–465. Bibcode:1997HETox..16..460M. doi:10.1177/096032719701600807. PMID   9292286. S2CID   44772701.
  12. 1 2 Tabangcura Jr D, Daubert GP. "British anti-Lewisite". Archived from the original on 2009-02-02.
  13. Peters RA, Stocken LA, Thompson RH (1945). "British anti-lewisite (BAL)". Nature. 156 (3969): 616–619. Bibcode:1945Natur.156..616P. doi:10.1038/156616a0. PMID   21006485. S2CID   4129186.