Succimer is indicated for the treatment of lead poisoning in children with blood level measured above 45 μg/dL. The use of dimercaptosuccinic acid is not approved for prevention of lead poisoning in anticipation of exposure in known lead-contaminated environments. Dimercaptosuccinic acid can cross the blood–brain barrier of mice,[11] but it is not known if this is also the case in humans.[12] Even if dimercaptosuccinic acid cannot reverse the damages done to the central nervous system, it might prevent further deterioration.[13]
Succimer facilitates urinary excretion of lead, and with sufficiently aggressive treatment, can reduce lead content in the brain.[14] It also increases urinary excretion of copper and zinc.[15] Dimercaptosuccinic acid improved cognitive function in rats that had been exposed to lead, but reduced cognitive function in rats that had not been exposed to lead.[14]
Succimer is an isomer of 2,3-dimercaptosuccinic acid. 2,3-dimercaptosuccinic acid is the organosulfur compound with the formulaHO2CCH(SH)CH(SH)CO2H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms.
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.
Dimercaptosuccinic acid was first synthesized by V. L. Nirenburg in the Urals Polytechnic Institute, commissioned by one of the electrical enterprises of Sverdlovsk, Russia, which consumed many tons of mercury and was looking for a medicine to prevent poisoning of personnel. In 1957, Chinese scientists found that dimercaptosuccinic acid can effectively treat antimony poisoning due to overdose of tartar emetic.[18] Pronounced protective effect in animal poisoning with arsenic and mercury was first shown by I. E. Okonishnikova in 1962. In 1984, the now-defunct Bock Pharmaceutical Company requested the FDA grant approval for orphan drug status under the brand name Chemet and the FDA approved of this in 1991, providing exclusivity until 1998 which was conveyed to the successor Sanofi in 1996.[19][20]
^Miller AL (June 1998). "Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity". Alternative Medicine Review. 3 (3): 199–207. PMID9630737.
^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.
^Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 472. ISBN9781284057560.
^Aaseth J, Jacobsen D, Andersen O, Wickstrøm E (March 1995). "Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review". The Analyst. 120 (3): 853–854. Bibcode:1995Ana...120..853A. doi:10.1039/an9952000853. PMID7741240.
^Clarkson TW, Magos L, Myers GJ (October 2003). "The toxicology of mercury--current exposures and clinical manifestations". The New England Journal of Medicine. 349 (18): 1731–1737. doi:10.1056/nejmra022471. PMID14585942.
^US 4550193, Lindemann MK, Lukenbach ER, "Process for the preparation of 2,3-dimercaptosuccinic acid and its lower alkyl esters", issued 29 October 1985, assigned to Johnson & Johnson Baby Products
^Liang Y, Chu C, Tsen Y, Ting K (1957). "Studies on antibilharzial drugs. Vl. The antidotal effects of sodium dimercaptosuccinate and BAL-glucoside against tartar emetic". Acta Physiol. Sin. 21: 24–32.
Aposhian HV, Aposhian MM (1990). "meso-2,3-Dimercaptosuccinic acid: chemical, pharmacological and toxicological properties of an orally effective metal chelating agent". Annual Review of Pharmacology and Toxicology. 30 (1): 279–306. doi:10.1146/annurev.pa.30.040190.001431. PMID2160791.
