Succimer 2,3-dimercaptosuccinic

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. 

Succimer (2,3-dimercaptosuccinic add, Chemet) is an orally effective chelator that is chemically similar to dimercaprol but contains two carboxylic acids that modify both the distribution and chelating spectrum of the drug. 

Initial treatment of the acute phase of lead intoxication involves supportive measures. Prevention of further exposure is important. Seizures are treated with diazepam or phenytoin (see Chapter 19), fluid and electrolyte balances must be maintained, and cerebral edema is treated with mannitol and dexamethasone or controlled hyperventilation. The concentration of lead in blood should be determined or at least a blood sample obtained for analysis prior to initiation of chelation therapy. Chelation therapy is indicated in symptomatic patients or in patients with a blood lead concentration in excess of 50-60 pg/dL (about 2.5 pM). Four chelators are employed edetate calcium disodium (CaNa EDTA), dimercaprol, D-penicillamine, and succimer (2,3-dimercaptosuccinic acid [DMSA], chemet). CaNa EDTA and dimercaprol usually are used in combination for lead encephalopathy. 

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. 

B. Succimer Succimer (2.3-dimercaptosuccinic acid DMSA) is a water-soluble bidentate congener of dimercaprol with oral bioavailability. 

Laughlin NK University of Wisconsin, Madison, Wl Validate the efficacy of chelation agents such as succimer (dimercaptosuccinic acid, DMSA) not only to reduce body lead stores in young children but also to alleviate neurobehavioral and target organ toxicity (Rhesus monkey) National Institute of Environmental Health Sciences... 

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). 

Medical treatment with chelation uses four different agents British Anti-Lewisite (2,3-dimercaptopropanol), edetate calcium disodium, D-penicillamine, and succimer or meso-2,3-dimercaptosuccinic acid (Roper et al. 1993). British Anti-Lewisite is contraindicated in children allergic to peanuts and in glucose-6-phosphate dehydrogenase deficiency D-penicillamine is contraindicated in penicillin allergy (Roper et al. 1993). 

Cremin et al. (1999) investigated the efficacy of chelation of lead with meso-2,3-dimercaptosuccinic acid in reducing the lead levels in the brain and its neurotoxicity from chronic oral exposure of the metal in adult rhesus monkeys. Their data, however, indicated that under the conditions of their study succimer treatment did not reduce brain lead levels in the primate model and also the limitations in the use of blood-lead level as an indicator of treatment efficacy. 

Once patients are hemodynamically stable and gastrointestinal symptoms have subsided, parenteral chelation may be changed to oral chelation with either oral unithiol, or oral succimer (DMSA, 2-3 dimercaptosuccinic acid see p 501). A suggested dose of unithiol is 4-8 mg/kg orally every 6 hours. Alternatively, give succimer 7.5 mg/kg orally every 6 hours, or 10 mg/kg orally every 8 hours. 

A. Oral. Succimer, meso-2,3-dimercaptosuccinic acid, DMSA (Chemet), 100-mg capsules in bottles of 100. 

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. 

Dimercaptosuccinic acid (DMSA, Succimer) can also be used to chelate arsenic (Graziano et al., 1978). 23-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). 

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