2, 3-Dimercaptosuccinic acid

BAL is the standard treatment for poisoning by arsenic compounds and will alleviate some effects from exposure to arsenic vesicants. It may also decrease the severity of skin and eye lesions if applied topically within minutes after decontamination is complete (i.e., within 2-5 minutes postexposure). Additional chelating agents for the treatment of systemic arsenic toxicity include meso-2,3-dimercaptosuccinic acid (DMSA) and 2,3-dimercapto-l-propanesulfonic acid (DMPS). 

Chen, S. et al., Persistent effect of in utero meso-2,3-dimercaptosuccinic acid (DMSA)on immune function and lead-induced immunotoxicity, Toxicology 132,67, 1999. 

Treatment of acute arsenic poisoning includes removal from the exposure source, supportive measures for loss of fluids, and chelation therapy (Ibrahim et al., 2006). Chelators that can be used include dimercaprol or 2,3-dimercaptosuccinic acid. In cases of renal failure, hemodialysis should be considered. 

Complex 2 also reacts directly with 2,3-dimercapto-l-propanol, or meso-2,3-dimercaptosuccinic acid to give 215 (as a mixture of cis/trans isomers) and 216, respectively.65... 

Henninghausen G, Merkord J. 1985. Meso-2,3-dimercaptosuccinic acid increases the inhibition of glutathione S-transferase activity from rat liver cytosol supernatants by di-n-butyltin dichloride. Arch Toxicol 57 67-68. 

Ercal N, Treeratphan P, Hammond TC, Matthews RH, Grannemann NH, et al. 1996. In vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-Dimercaptosuccinic Acid or N-acetylcysteine. Free Radical Biol Med 21 157-161. 

Flora, S.J.S. (1999). Arsenic induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3 dimercaptosuccinic acid in rats. Clin. Exp. Pharmacol. Physiol. 26 865-9. 

Flora, S.J.S., Mehta, A., Rao, P.V.L., Kannan, G.M., Bhaskar, A.S.B., Dube, S.N., Pant, B.P. (2004a). Therapeutic potential of monoisoamyl and monomethyl esters of meso 2,3-dimercaptosuccinic acid in gallium arsenide intoxicated rats. Toxicology 195 127-46. 

Karman, G.M., Flora, S.J.S. (2004). Combined administration of meso 2,3-dimercaptosuccinic acid (DMSA) or monoisoamyl DMSA with an antioxidant for the treatment of chronic experimental arsenic poisoning in rats. Ecotoxicol. Environ. Saf. 58 37-43. 

Saxena, G., Pathak, U., Flora, S.J.S. (2005). Beneficial role of monoesters of meso 2,3-dimercaptosuccinic acid in the mobilization of lead and recovery of tissue oxidative injury in rats. Toxicology 214 39-56. 

A chelator should be given if there is dyspnea, pulmonary edema, or skin bums larger than pahn size (Goldfrank et al, 2002). BAL is the traditional arsenic chelator, but it has numerous side effects. The deep intramuscular injections are very painful and BAL can cause hypertension, tachycardia, and vomiting. 2,3-Dimercaptosuccinic acid (DMSA, Succimer ) can also be used to chelate arsenic (Graziano et al, 1978). 2,3-Dimercapto-l-propanesulfonic acid (DMPS) is used in Europe and has been effective in protecting rabbits from the lethal effects of lewisite (Aposhian et al, 1982). 

In severe lead poisoning sodium calciumedetate is commonly used to initiate lead excretion. It chelates lead from bone and the extracellular space and urinary lead excretion of diminishes over 5 days thereafter as the extracellular store is exhausted. Subsequently symptoms (colic and encephalopathy) may worsen and this has been attributed to redistribution of lead from bone to brain. Dimercaprol is more effective than sodium calciumedetate at chelating lead from the soft tissues such as brain, which is the rationale for combined therapy with sodium calciumedetate. More recently succimer (2,3-dimercaptosuccinic acid, DMSA), a water-soluble analogue of dimercaprol, has been increasingly used instead. Succimer has a high affinity for lead, is suitable for administration by mouth and is better tolerated (has a wider therapeutic index) than dimercaprol. It is licenced for such use in the USA but not the UK. 

Glotzer DE. The current role of 2,3-dimercaptosuccinic acid (DMSA) in the management of childhood lead poisoning. Drug Saf 1993 9(2) 85-92. 

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