ARE WE READY TO REPLACE DIMERCAPROL (BAL) AS AN ARSENIC ANTIDOTE

1 Dimercaprol (BAL), 2,3-dimercaptopropanesulphonate sodium (DMPS) and meso-2,3-dimercaptosuccinic acid (DMSA) are effective arsenic antidot es, but the question which one is preferable for optimal therapy of ar senic poisoning is still open to discussion. Major drawbacks of BAL in clude (a) its low therapeutic index, (b) its tendency to redistribute arsenic to brain and testes, for example, (c) the need for (painful) i ntramuscular injection and (d) its unpleasant odour. 2 The newer antid otes DMPS and DMSA feature low toxicity and high therapeutic index. Th ey can be given orally or intravenously due to their high water solubi lity. While these advantages make it likely that DMPS and DMSA will re place BAL for the treatment of chronic arsenic poisoning, acute intoxi cation - especially with lipophilic organoarsenicals - may pose a prob lem for the hydrophilic antidotes, because their ionic nature can adve rsely affect intracellular availability. 3 This article focuses on asp ects dealing with the power of BAL, DMPS, and DMSA to mobilize tissue- bound arsenic in various experimental models, such as monolayers of MD CK (=Madin-Darby canine kidney) cells from dog kidney, isolated perfus ed liver from guinea-pigs, and perfused jejunal segments from rat smal l intestine. 4 The results show that hydrophilic DMPS and DMSA may fai l to rapidly and completely remove arsenic that has escaped from the e xtracellular space across tight epithelial barriers. However, owing to their low toxicity, which allows larger doses to be applied, and the potential modification of their pharmacokinetics by means of inert ora l anion-exchange resins, DMPS and DMSA may advantageously replace BAL whenever intervention time is not critical. With severe intoxication b y organic arsenicals, when the point-of-no-return is a limiting factor , BAL may still have a place as an arsenic antidote.