Dimercaprol
Encyclopedia
Dimercaprol or British anti-Lewisite (abbreviated BAL), is a compound developed by British biochemists at Oxford University during World War II
. It was developed secretly as an antidote for lewisite
, the now-obsolete arsenic
-based chemical warfare agent. Today, it is used medically in treatment of arsenic
, mercury
, gold
and lead
, and other toxic metal poisoning
. In addition, it has in the past been used for the treatment of Wilson's disease
, a genetic disorder in which the body tends to retain copper
.
and some other heavy metals act by chemically reacting with adjacent thiol
residues on metabolic enzymes, creating a chelate complex that inhibits the affected enzyme's activity. Dimercaprol competes with the thiol groups for binding the metal ion, which is then excreted in the urine.
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
. Serious side effects include nephrotoxicity
and hypertension
.
Dimercaprol has been found to form stable chelates in vivo with many other toxic 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 phenyl mercury toxicity. Dimercaprol also enhances the toxicity of selenium
and tellurium, so it is not to be used to remove these metals from the body.
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
. It was developed secretly as an antidote for lewisite
Lewisite
Lewisite is an organoarsenic compound, specifically an arsine. It was once manufactured in the U.S. and Japan as a chemical weapon, acting as a vesicant and lung irritant...
, the now-obsolete arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
-based chemical warfare agent. Today, it is used medically in treatment of arsenic
Arsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
, mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
and lead
Lead
Lead is a main-group element in the carbon group with the symbol Pb and atomic number 82. Lead is a soft, malleable poor metal. It is also counted as one of the heavy metals. Metallic lead has a bluish-white color after being freshly cut, but it soon tarnishes to a dull grayish color when exposed...
, and other toxic metal poisoning
Toxic metal
Toxic metals are metals that form poisonous soluble compounds and have no biological role, i.e. are not essential minerals, or are in the wrong form. Often heavy metals are thought as synonymous, but lighter metals also have toxicity, such as beryllium, and not all heavy metals are particularly...
. In addition, it has in the past been used for the treatment of Wilson's disease
Wilson's disease
Wilson's disease or hepatolenticular degeneration is an autosomal recessive genetic disorder in which copper accumulates in tissues; this manifests as neurological or psychiatric symptoms and liver disease...
, a genetic disorder in which the body tends to retain copper
Copper
Copper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
.
Biochemical function
ArsenicArsenic
Arsenic is a chemical element with the symbol As, atomic number 33 and relative atomic mass 74.92. Arsenic occurs in many minerals, usually in conjunction with sulfur and metals, and also as a pure elemental crystal. It was first documented by Albertus Magnus in 1250.Arsenic is a metalloid...
and some other heavy metals act by chemically reacting with adjacent thiol
Thiol
In organic chemistry, a thiol is an organosulfur compound that contains a carbon-bonded sulfhydryl group...
residues on metabolic enzymes, creating a chelate complex that inhibits the affected enzyme's activity. Dimercaprol competes with the thiol groups for binding the metal ion, which is then excreted in the urine.
Dimercaprol is itself toxic, with a narrow therapeutic range
Therapeutic index
The therapeutic index is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death or toxicity ....
and a tendency to concentrate arsenic in some organs. Other drawbacks include the need to administer it by painful intramuscular injection
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...
. Serious side effects include nephrotoxicity
Nephrotoxicity
Nephrotoxicity is a poisonous effect of some substances, both toxic chemicals and medication, on the kidneys. There are various forms of toxicity. Nephrotoxicity should not be confused with the fact that some medications have a predominantly renal excretion and need their dose adjusted for the...
and hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
.
Dimercaprol has been found to form stable chelates in vivo with many other toxic metals including inorganic mercury
Mercury (element)
Mercury is a chemical element with the symbol Hg and atomic number 80. It is also known as quicksilver or hydrargyrum...
, antimony
Antimony
Antimony is a toxic chemical element with the symbol Sb and an atomic number of 51. A lustrous grey metalloid, it is found in nature mainly as the sulfide mineral stibnite...
, bismuth
Bismuth
Bismuth is a chemical element with symbol Bi and atomic number 83. Bismuth, a trivalent poor metal, chemically resembles arsenic and antimony. Elemental bismuth may occur naturally uncombined, although its sulfide and oxide form important commercial ores. The free element is 86% as dense as lead...
, cadmium
Cadmium
Cadmium is a chemical element with the symbol Cd and atomic number 48. This soft, bluish-white metal is chemically similar to the two other stable metals in group 12, zinc and mercury. Similar to zinc, it prefers oxidation state +2 in most of its compounds and similar to mercury it shows a low...
, chromium
Chromium
Chromium is a chemical element which has the symbol Cr and atomic number 24. It is the first element in Group 6. It is a steely-gray, lustrous, hard metal that takes a high polish and has a high melting point. It is also odorless, tasteless, and malleable...
, cobalt
Cobalt
Cobalt is a chemical element with symbol Co and atomic number 27. It is found naturally only in chemically combined form. The free element, produced by reductive smelting, is a hard, lustrous, silver-gray metal....
, gold
Gold
Gold is a chemical element with the symbol Au and an atomic number of 79. Gold is a dense, soft, shiny, malleable and ductile metal. Pure gold has a bright yellow color and luster traditionally considered attractive, which it maintains without oxidizing in air or water. Chemically, gold is a...
, and nickel
Nickel
Nickel is a chemical element with the chemical symbol Ni and atomic number 28. It is a silvery-white lustrous metal with a slight golden tinge. Nickel belongs to the transition metals and is hard and ductile...
. 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 phenyl mercury toxicity. Dimercaprol also enhances the toxicity of selenium
Selenium
Selenium is a chemical element with atomic number 34, chemical symbol Se, and an atomic mass of 78.96. It is a nonmetal, whose properties are intermediate between those of adjacent chalcogen elements sulfur and tellurium...
and tellurium, so it is not to be used to remove these metals from the body.
See also
- Chelation therapyChelation therapyChelation therapy is the administration of chelating agents to remove heavy metals from the body. For the most common forms of heavy metal intoxication—those involving lead, arsenic or mercury—the standard of care in the United States dictates the use of dimercaptosuccinic acid...
- Chemical warfare agent
- Toxic metal poisoningToxic metalToxic metals are metals that form poisonous soluble compounds and have no biological role, i.e. are not essential minerals, or are in the wrong form. Often heavy metals are thought as synonymous, but lighter metals also have toxicity, such as beryllium, and not all heavy metals are particularly...