Succimer (meso-2,3-Dimercaptosuccinic Acid): A Comprehensive Pharmacological and Clinical Monograph

1.0 Executive Summary

1.1 Overview of Succimer as a Chelating Agent

Succimer is an orally active, small molecule dithiol compound that functions as a heavy metal chelating agent.[1] Structurally, it is a water-soluble analog of dimercaprol (BAL) and is classified as a sulfur-containing dicarboxylic acid.[1] Its primary therapeutic role is as an antidote in the management of heavy metal poisoning. The molecule's efficacy stems from its ability to form stable, water-soluble complexes, or chelates, with toxic metal ions. These complexes are subsequently eliminated from the body, primarily through renal excretion, thereby reducing the overall metal burden and mitigating toxicity.[4]

1.2 Key Therapeutic Indications and Mechanism of Action

The United States Food and Drug Administration (FDA) has approved succimer for the treatment of lead poisoning in pediatric patients who present with blood lead levels (BLL) exceeding 45 µg/dL.[6] It is important to note that the drug is not indicated for the prophylaxis of lead poisoning in individuals who may be exposed to a lead-containing environment.[1] The mechanism of action is centered on the two sulfhydryl (mercapto) groups within the succimer molecule. These groups exhibit a high affinity for divalent and trivalent metal cations, binding to them to form a stable heterocyclic ring structure. This sequestration prevents the metal ions from interacting with and damaging essential biological macromolecules, such as enzymes.[6] While its primary indication is for lead poisoning, succimer is also used off-label for the treatment of mercury and arsenic poisoning.[1]

1.3 Summary of Pharmacokinetic Profile and Clinical Efficacy