DMSA, DMPS AND OTHER ORALLY ACTIVE DITHIOL CHELATORS

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Since 1956, DMPS and DMSA, water soluble analogs of BAL, have replaced this chelating agent in Soviet and mainland China medicine. The analogs are less toxic and are effective orally. Meaningful information about the metabolism and biotransformation of these agents, which are new to the western world, is lacking because analytical techniques for quantitatively assaying and/or identifying them is nonexistent. We plan to develop HPLC, GC/MS and other assays for these dimercapto compounds and their derivatives. Once this is done we shall investigate the metabolic liability and biotransformation of DMPS, DMSA and DMPA. In addition, the therapeutic effectiveness of DMPS, DMSA, DMPA and WR2721 will be studied as antidotes for chronic and acute lead poisoning, for cis-platinum (a cancer chemotherapy agent) renal toxicity and, eventually, for poisoning by compounds of other metals. A synthetic fragment of metallothionein will be tested in tissue culture as an antidote to sodium arsenite. Experiments in which DMPS, DMSA and DMPA have been compared at the same time or by the same investigative group are nonexistent except in the case of sodium arsenite as performed in the principal investigator's laboratory. With the increasing pollution of the environment by heavy metals, better metal binding agents need to be developed and studied. They should be available to help decrease the severity of any illness due to environmental pollution with heavy metals or to any other poisoning by heavy metals. Both in vitro and in vivo techniques will be used to investigate the questions being asked.