Optical isomers of 2,3-dimercapto-1-propanesulfonate: antidotal activity, in vitro and in vivo, against sodium arsenite

CA Hsu, HV Aposhian, S Heydolph and W Parr

DMPS (2,3-dimercapto-1-propanesulfonate, Na salt) is an important water soluble analog of dimercaprol. All investigations of this antidote for heavy metal intoxication have dealt only with the racemic mixture. In the present report, the optical isomers of DMPS have been separated and the arsenic-antidote activity of the levo-rotatory (-)-isomer, the dextro-rotatory (+)-isomer and the racemic mixture of DMPS have been investigated in vivo and in vitro. The individual optical isomers and the racemic mixture of DMPS are effective equally, in vitro, in preventing the inhibition by sodium arsenite of the activity of mouse kidney pyruvate dehydrogenase complex. In addition, when pyruvate dehydrogenase is inhibited, in vitro, by sodium arsenite, any of the three DMPS preparations will reverse the inhibition equally well. The in vitro evidence suggests that two molecules of DMPS are required to prevent the effects of one molecule of sodium arsenite. Neither the LD50 nor the ED50 values of each of the three forms of DMPS differ significantly when measured i.p. in mice. In addition, there is no striking difference between the effectiveness of the levo- or dextro- rotatory DMPS when given orally to mice challenged with sodium arsenite. Thus, the use of the individual optical isomers of DMPS does not appear to have any advantage over the racemic mixture as an arsenic antidote under these conditions.

Volume 224, Issue 2, pp. 314-318, 02/01/1983
Copyright © 1983 by American Society for Pharmacology and Experimental Therapeutics