Toxicology – Antidotes: Chelating Agents

Overview

Chelators bind specific toxic metals and form complexes that can be eliminated from the body, usually through the urine. The appropriate agent depends on the metal involved and the severity of poisoning.

Succimer (DMSA)

Binds: Lead, arsenic, and mercury.

Mechanism of Action

• Water-soluble compound related to dimercaprol (BAL)
• Contains sulfhydryl groups that bind toxic metals
• The resulting complexes are primarily excreted in urine
• Has only limited effectiveness for cadmium removal

Succimer is commonly used as an oral chelator, particularly for selected cases of lead poisoning.

DMPS (2,3-Dimercapto-1-Propanesulfonic Acid)

Binds: Mercury and arsenic; it can also bind lead.

Mechanism of Action

• Water-soluble dimercaprol-related chelator
• Sulfur-containing groups bind metal ions
• Metal-chelator complexes are eliminated mainly through the kidneys

Availability and approved indications vary by country.

Penicillamine

Binds: Primarily copper; it has also been used in selected cases involving other metals.

Mechanism of Action

• A penicillin-related compound without antibacterial activity
• Acts as a thiol-containing chelator
• Binds free copper and reduces its ability to participate in damaging oxidation-reduction reactions
• Excreted in urine

It is particularly associated with treatment of copper overload, including Wilson disease.

Calcium Disodium EDTA (CaNa₂EDTA)

Binds: Lead.

Mechanism of Action

• Primarily acts in the extracellular compartment
• Binds circulating lead and promotes its urinary elimination
• As circulating lead decreases, additional lead can redistribute from tissues into the blood and become available for chelation

The calcium disodium form is used for lead poisoning; plain disodium EDTA can cause dangerous hypocalcemia.

Deferoxamine (DFO)

Binds: Iron.

Mechanism of Action

• Chelates free ferric iron
• Forms the water-soluble complex ferrioxamine
• Mainly targets free or loosely bound iron rather than iron incorporated into hemoglobin
• The complex is eliminated through urine

Deferoxamine is an important antidote for significant acute iron poisoning.

Dimercaprol (BAL – British Anti-Lewisite)

Binds: Arsenic, mercury, and lead; historically developed for the arsenical warfare agent Lewisite.

Mechanism of Action

• Contains sulfhydryl (–SH) groups that bind toxic metals
• Prevents metals from interacting with sulfhydryl-containing cellular proteins
• Metal-chelator complexes are eliminated primarily through urine

Key Points

• Lead: Succimer or CaNa₂EDTA; dimercaprol may be added in severe cases.
• Arsenic/Mercury: Dimercaprol, succimer, or other specialist-selected thiol chelators.
• Copper: Penicillamine.
• Iron: Deferoxamine.
• Chelation should be guided by the specific metal, blood concentration, clinical severity, and toxicology consultation.