[medical citation needed]

Dimercaprol
Iupac name2,3-Bis(sulfanyl)propan-1-ol[1]
TradenameBAL in Oil
DailymedidDimercaprol
Pregnancy usC
Routes of administrationintramuscular
Legal usRx-only
ExcretionUrine[2]
Cas number59-52-9
Atc prefixV03
Atc suffixAB09
Pubchem3080
DrugbankDB06782
Chemspiderid2971
Unii0CPP32S55X
KeggD00167
Chembl1597
Synonyms2,3-Dimercaptopropanol
British Anti-Lewisite
2,3-Dithiopropanol
2,3-Dimercaptopropan-1-ol
British antilewisite
C3
H8
O1
S2
SmilesOCC(S)CS
Stdinchi1S/C3H8OS2/c4-1-3(6)2-5/h3-6H,1-2H2
StdinchikeyWQABCVAJNWAXTE-UHFFFAOYSA-N
Density1.239
Boiling point393
Boiling notesat 2.0 kPa

Dimercaprol, also called British anti-Lewisite (BAL), is a medication chelator 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]

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 organometallic 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 chelating the zinc ions needed for the activity of 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 urinary excretion of cadmium, use in case of cadmium toxicity is to be avoided as the drug-cadmium complex is rather nephrotoxic. It does, however, remove inorganic mercury from the kidneys; Dimercaprol should not be used to treat organomercury poisoning. 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 organoarsenic chemical warfare agent.[12]

See also

References

  1. ^ 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.
  2. ^ Poisoning in Children. Jaypee Brothers Publishers. 2013. p. 70. ISBN 978-93-5025-773-9.
  3. ^ "Dimercaprol". The American Society of Health-System Pharmacists. Archived 21 December 2016 at the Wayback Machine. Retrieved 8 December 2016.
  4. ^ ((World Health Organization)) (2009). 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 2016-12-20 at the Wayback Machine.
  6. ^ ((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. ^ 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, Evans C, Wilkinson MC, Harrison RA, Kool J, Casewell NR (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. ^ Tabangcura Jr D, Daubert GP. "British anti-Lewisite". Archived 2009-02-02 at the Wayback Machine.
  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