Dimercaptosuccinic acid, lead poisoning

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. 

Aaseth J, Jacoben D, Andersen O and Wick-STE0M E (1995) Treatment of mercury and lead poisoning with dimercaptosuccinic Acid (DMSA) and sodium dimercaptopropanesulfonate (DMPS). Analyst 120 853-854. 

Chelation therapy often is begun with dimercaprol (3—4 mg/kg intramuscularly every 4—12 hours) until abdominal symptoms subside and charcoal (if given initially) is passed in the feces. Oral treatment with penicillamine then may be substituted for dimercaprol and continued for 4 days. Penicillamine is given in 4 divided doses to a maximum of 2 g/day. If symptoms recur after cessation of chelation therapy, a second course of penicillamine may be instituted. Succimer (2,3-dimercaptosuccinic acid), a derivative of dimercaprol, is efficacious in the treatment of arsenic poisoning but is FDA-approved only for lead chelation in children. 

Treatment of lead-poisoned animals usually involves the removal of ingested lead objects and application of antibiotics. For example, a captive bottlenose dolphin that had 40 lead-containing air pellets in its second stomach, as determined by radiography, was treated with 250.0 mg penicillamine/kg BW given orally three times daily for 5 days after the pellets had been removed from the stomach using an endoscope. Anemia in chimpanzees is sometimes associated with lead toxicity. In one case, a 19-year-old female chimpanzee with a history of excessive menstrual bleeding had a blood serum level of 1.03 mg Pb/L. The animal was successfully treated using oral chelation therapy 2,3-dimercaptosuccinic acid at 10.0 mg/kg BW per os for 5 days, then lO.Omg/kg BW for 2 weeks. 

Goyer RA, Rhyne B (1973) Pathological effects of lead. Int Rev Exp Pathol 12 1-77 Grandjean P, Jacobsen lA, Jorgensen PJ (1991) Chronic lead poisoning treated with dimercaptosuccinic acid. Pharmacol Toxicol 68 266-269... 

Another dimercapto chelating agent commonly used to treat lead poisoning is 2,3-dimercaptosuccinic acid (DMSA), also known as succimer or Chemet. Its structure is shown in Figure 6.8a. The primary advantage of succimer is that it can be administered orally. Like BAL, it is also effective against arsenic poisoning. 

Fox, D. A., Overmann, S. R. and Wooley, D. E. (1979). Neurobehavloral ontogeny of neonatal lead-exposed rats. 11. Maximal electroshock seizures in developing and adult rats. Neuroto dcol. 1, 149-170. Friedheim, E., Graziano, J. H., Popovac, D., Dragovic, D. and Kaul, B. (1978). Treatment of lead poisoning by 2,3-dimercaptosuccinic acid. Lancet 2, 1234-1236. 

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