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© 1984 Oxford University Press

research-article

DMSA, DMPS, and DMPA—as Arsenic Antidotes1

H. VASKEN APOSHIAN*, DEAN E. CARTER{dagger}, TODD D. HOOVER{dagger}, CHIN-AN HSU*, RICHARD M. MAIORINO* and ERIC STINE{dagger}

*Department of Cellular and Developmental Biology, University of Arizona Tucson, Arizona 85721 {dagger}Department of Pharmacology and Toxicology, University of Arizona Tucson, Arizona 85721

DMSA, DMPS, and DMPA—as Arsenic Antidotes. APOSHIAN, H. V., CARTER, D. E., HOOVER, T. D., HSU, C.-A., MAIORINO, R. M., AND STINE, E. (1984). Fundam. Appl. Toxicol. 4, S58–S70. meso-Dimercaptosuccinic acid (DMSA), 2,3-dimercapto-1-propanesulfonic acid, Na salt (DMPS), and N-(2,3-dimercaptopropyl)-phthalamidic acid (DMPA) are water soluble analogs of 2,3-dimercapto-1-propanol (BAL). The relative effectiveness or therapeutic index of these dimercapto compounds in protecting mice from the lethal effects of an LD99 of sodium arsenite is DMSA > DMPS > DMPA > BAL in the magnitude of 42:14:4:1, respectively. DMPS, DMPA, or DMSA will mobilize tissue arsenic. BAL, however, increases the arsenic content of the brain of rabbits injected with sodium arsenite. These results raise the question as to the appropriateness of BAL as the treatment for systemic arsenic poisoning. Either DMSA or DMPS, when given sc or po, will protect rabbits against the lethal systemic effects of subcutaneously administered Lewisite. DMPS and DMSA have promise as prophylactics for the prevention of the vesicant action of Lewisite. The sodium arsenite inhibition of the pyruvate dehydrogenase (PDH) complex can be prevented and reversed in vitro or in vivo by DMPS, DMSA, DMPA, or BAL. Of them all, DMPS is most potent and BAL appears to be the least potent. The usefulness of all these dimercapto compounds would be enhanced by a careful study of their metabolism and bio-transformation. These dimercapto compounds are in a great many respects orphan drugs. At this stage of their development, it is very difficult for the clinician to obtain funds to study them clinically even though they appear to be useful for treatment of poisoning by any one of the heavy metals.


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