Some science behind the scenes
Dimercaptosuccinic acid (DMSA), is the organosulfur compound with the formula HO2CCH(SH)CH(SH)CO2H. It occurs in two diastereomers, meso and the chiral dl forms.
The meso isomer is used as a chelating agent. The acid is most often used as a treatment for heavy metal toxicity. Meso 2,3-dimercaptosuccinic acid binds to "soft" heavy metals such as Hg2+ and Pb2+, mobilizing these ions for excretion. It binds to metal cations through the thiol groups, which ionize upon complexation.
The main metals that can be chelated by DMSA are mercury, antimony, arsenic, and lead.
DMSA was first synthesized by V. Nirenburg in the Urals Polytechnic Institute, commissioned by one of the electrical enterprises of Sverdlovsk, which consumed many tons of mercury and was looking for a medicine to prevent poisoning of personnel.
In 1957, it was found by Chinese scientists that DMSA can effectively treat antimony poisoning due to overdose of tartar emetic.
Pronounced protective effect in animal poisoning with arsenic and mercury was first shown by I. Okonishnikova in 1962.
Dimercaptosuccinic acid (known commercially as CHEMET) is indicated for the treatment of lead poisoning in children with blood level measured above 45 µg/dL. [The use of DMSA is not approved for prophylactic/prevention of lead poisoning in anticipation of exposure in known lead contaminated environments]. Its elimination half-life is 2.5-3.5 h. DMSA can cross the blood–brain barrier of mice, but not that of humans, limiting its use to extracting heavy metals from parts of the body other than the central nervous system.
Another application for DMSA is for provocation of tissue heavy metals in anticipation of a urine test. This is sometimes called a "challenge" or "provoked" heavy metals test.
DMSA is used to help mobilize heavy metals stored in body tissues (and therefore not typically present in the circulation) and increase the excretion of heavy metals in the urine. In a study by Howard Frumkin et al., this sort of test was shown to not reliably provide an indication of past chronic mercury exposure, something it was often used for.
A 2004 study by GP Archbold, et al. called the results of a DMSA challenge test "misleading" for the purposes of diagnosing mercury toxicity. Moreover, DMSA share the limitation of extracellular distribution, which makes it unable to cross the cell membrane and chelate heavy metals from intracellular sites.
The relative activities of a series of novel monoalkyl esters of meso-2,3-dimercaptosuccinic acid (MiADMSA) have been examined as agents for the mobilization of cadmium, lead and arsenic owing to the ability of these monoesters to cross cell membranes.
The monoesters were found to be more effective than the parent compound DMSA. The complexes (monoesters of DMSA) seem to penetrate cells (not possible in the case of DMSA), which helps in targeting intracellular sites in the body and aids in the removal of toxic metal ions in the cytosol and organelles inside the cell.
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- A safe strategy to decrease fetal lead exposure in a woman with chronic intoxication
- Arsenic and drinking water, chelation therapy
- Cadmium, Lead and DMSA chelation
- Description of 3,180 courses of chelation with dimercaptosuccinic acid in children ≤ 5 y with severe lead poisoning in Zamfara, Northern Nigeria: a retrospective analysis of programme data
- EDTA redistribution of lead and cadmium into the soft tissues in a human with a high lead burden - should DMSA always be used to follow EDTA in such cases?
- Effects of chelators on mercury, iron, and lead neurotoxicity in cortical culture
- Garlic and heavy metal poisoning
- How to Rid Your Body of Mercury and Other Heavy Metals: A 3-Step Plan to Recover Your Health
- In vitro assessment of chelating agents with regard to their abstraction efficiency of Cd(2+) bound to plasma proteins
- meso-2,3-Dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent
- The role of thiols, dithiols, nutritional factors and interacting ligands in the toxicology of mercury