Chelating agents BAL

Besides stopping the exposure to mercury and medically treating the symptoms, as in cases of acute or chronic mercury intoxication, the renal and fecal excretion of mercury may be increased by the application of a chelating agent. BAL (British Anti-Lewisite, Dimercaprol) is still used for this purpose in some countries, but has several disadvantages compared with more effective, water-soluble derivatives such as 2,3-dimer-... 

Figure 12-7. Proposed sites of inhibition (0) of the respiratory chain by specific drugs, chemicals, and antibiotics. The sites that appear to support phosphorylation are indicated. BAL, dimercaprol. TTFA, an Fe-chelating agent. Complex I, NADHiubiquinone oxidoreductase complex II, succinate ubiquinone oxidoreductase complex III, ubiquinohferricytochrome c oxidoreductase complex IV, ferrocytochrome ctoxygen oxidoreductase. Other abbreviations as in Figure 12-4.

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). 

Treatment. Since the 1950s, the treatment of Wilson s disease has relied on chelating agents [25]. Early attempts to use BAL or EDTA for this purpose were unsuccessful, but penicillamine, triethylene tetramine dihydrochloride (trientine), and tetrathiomolybdate, all in combination with a low-copper diet, have proved to be effective, and result in the urinary excretion of large amounts of copper. The use of penicillamine is complicated by the fact that it may induce a transient worsening of neurologic function due to rapid mobilization of copper, and also has other side-effects, such as the development of nephrosis. Tetrathiomolybdate is an effective alternative with fewer side-effects [26]. In cases in which the dose was rapidly escalated, however, bone marrow suppression or liver function abnormalities have been described. 

Chelating agents are widely used as specific antidotes for heavy metals. They form stable, soluble, nontoxic complexes and in easily excreted form. They promote dissociation of bound metal from tissue enzymes and other functional macromolecules. These metal chelates are water soluble, e.g. EDTA, BAL, desferrioxamine etc. 

The first chelating agent developed as an antidote to a heavy metal poison was 2,3-dimereaptopropanol (dimercaprol, British Anti-Lewisite, BAL). Originally intended for use on victims of the arsenical vesicant poison gas Lewisite52, it has since proved efficacious in the treatment of antimony, gold and mercury poisoning as well as... 

As well as the above 2,3-dimercaptoalkanes a few other vicinal dithiols have also been sythesized. The interaction of methylmercury(II) with chelating agents such as BAL involves linear two-coordinate complexes and in only a few cases has chelation involved a bidentate ligand. In a search for evidence of thiol-containing bidentate chelation, Alcock et al.311 synthesized three sterically constrained dithiols - cyclohexane-1,2-dithiol, toluene-3,4-dithiol and bicyclo[2.2. l]heptane-2,3-dithiol - and demonstrated by spectroscopy and crystallography their formation of chelates with methylmercury(II) of the form (40). 

The most important chelating agents currently in use in the United States are described below. Dimercaprol (2,3-Dimercaptopropanol, BAL)... 

Copper toxicity has been observed, althongh it is not a function of dietary overload. Abnormally low levels of ceruloplasmin associated with the genetic disorder, Wilson s disease, lead to excessive deposition of copper in the central nervous system, ocular tissue, liver, and other organs. Severe psychotic symptoms are observed. Urinary excretion of the copper can be achieved with specific chelating agents such as British anti-lewisite (BAL, 2,3-dimercaptopropanol) or penicillamine, orally administered. Symptoms of the disease are reversed as the copper levels return to normal. Reduction of dietary copper nptake by competition with relatively high levels of oral zinc is also effective. ... 

One of the chemical derivatives of dimercaprol (BAL) is DMSA. DMSA is an orally active chelating agent, much less toxic than BAL, and its therapeutic index is about 30 times higher (Angle and Kuntzelman, 1989). The empirical formula of DMSA is C4H6O4S2 and its molecular weight is 182.21. It is a weak acid soluble in water. 

BAL is a chelating agent used in treating heavy metal poisoning. It acts as a bidentate ligand. What types of linkage isomers are possible when BAL coordinates to a metal ion ... 

British antilewisite (BAL) or dimercaprol was developed as an antidote for lewisite. It is used in medicine as a chelating agent for heavy metals. Although BAL can cause toxicity itself, evidence suggests that BAL in oil administered intramuscularly will reduce the systemic effects of lewisite. BAL skin and ophthalmic ointment decrease the severity of skin and eye lesions when applied immediately after early decontamination, but neither of these ointments is currently manufactured. 

There is no known useful treatment for methylmercury poisoning. A variety of chelating agents, such as D-penicillamine, l-acetyl-D,L-penicillamine, thiol resins, activated charcoal, BAL (British Antilewisite 2,3-dimercaptopropanol), and meso-2,3-dime-rcaptosuccinic acid, have been used to treat methyl-mercury exposure but with limited to no success. 

Clinical management is supportive. Gastric decontamination should be considered only in the case of massive ingestions. Normal zinc levels in the blood are between 68 and 136pgdl . Chelating agents such as BAL (British Antilewisite 2,3-dimercapto-propanol) or calcium EDTA will enhance removal of zinc, but are not likely indicated unless the unusual case of massive chronic exposure. Hemodialysis and other methods of extracorporeal elimination are not necessary. 

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