Lead chelation therapy agents

One of the greatest goals of this field is to develop a sufficiently good understanding of lead coordination chemistry to be able to rationally design improved ligands for lead that could be used as chelation therapy agents to treat... 

The thermodynamics of lead-ligand interactions provide key insights both into the probable mechanisms of lead s toxicity and into the design of improved chelation therapy agents. Various constants can be used to describe the affinity of a metal ion for a given ligand described by the net equilibrium (300, 301) ... 

The most commonly used chelation therapy agents in the United States today are EDTA and DMSA (or succimer). In addition, penicillamine (PCA) and BAL are used to chelate lead. Each of these agents has numerous disadvantages, ranging from undesirable methods of delivery (intramuscular injection of BAL and intravenous delivery of EDTA), to unpleasant side effects (typically nausea and vomiting), to chelation and increased excretion of necessary metals (e.g., iron and zinc) (Table XIX) (17, 207, 525). 

The treatment of thalassemia, as in other metal overload disorder, is chelation therapy. The chelating agent most widely nsed is deferoxamine administered subcutaneously. The search for an orally administered iron chelator has intensified in recent years, leading to cUnical trials of many potential new iron chelators snch as deferiprone(Ll). However, many issues regarding the nse of these drugs, such as dose-related toxicity and recommended age of initiation, remain unresolved. " ... 

It is axiomatic that the toxicity of the ligand selected for the treatment and any side effects, such as co-liberating essential metals during therapy, ought, collectively, to add up to less than the residual toxicity of the element that has been deposited in the body. However, factors other than simple toxicity or unpleasant side effects need to be considered. For example, about 90% of the lead accumulated in the human body is sequestered in non-toxic form in bone. Incautious chelation therapy with an agent like EDTA, or administration of large amounts of... 

The chelation therapy mentioned above works by aiming to reduce BLLs by introducing agents such as DMSA (dimercaptosuc-cinic acid) and EDTA (calcium disodium) which bind to lead and thereby encourage its excretion in the urine. DMSA is particularly useful in yoimger children as it can be given by mouth, it is not without side effects however which include anorexia, nausea, vomiting and rashes. It is more commonly indicated in patients... 

Once in the brain, lead cannot be removed by chemical chelating agents of the sort that Roberto received. This means that even after the lead levels in blood have been decreased by chelation therapy to apparently insignificant... 

Earlier we mentioned that chelation therapy is used in the treatment of lead poisoning. Other metals, such as arsenic and mercury, can also be removed using chelating agents. 

Penicillamine (Cuprimine), a derivative of penicillin, is officially classified as a chelating agent that is often used in the treatment of heavy metal intoxication (e.g., lead poisoning). In addition, this drug has been used in patients with severe rheumatoid arthritis, and seems to be as effective as other DMARDs such as methotrexate, sulfasalazine, and gold therapy.68 98 Penicillamine, however, tends to be substantially more toxic than other DMARDs, and is therefore used rarely in the treatment of specific patients with rheumatoid arthritis.68... 

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