Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity.

Heavy metals are, unfortunately, present in the air, water, and food supply. Cases of severe acute lead, mercury, arsenic, and cadmium poisoning are rare; however, when they do occur an effective, non-toxic treatment is essential. In addition, chronic, low-level exposure to lead in the soil and in residues of lead-based paint, to mercury in the atmosphere, in dental amalgams and in seafood, and to cadmium and arsenic in the environment and in cigarette smoke is much more common than acute exposure. Meso-2,3-dimercaptosuccinic acid (DMSA) is a sulfhydryl-containing, water-soluble, non-toxic, orally-administered metal chelator which has been in use as an antidote to heavy metal toxicity since the 1950s. More recent clinical use and research substantiates this compound s efficacy and safety, and establishes it as the premier metal chelation compound, based on oral dosing, urinary excretion, and its safety characteristics compared to other chelating substances.

Human studies with the chelating agents, DMPS and DMSA.

Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.