Succimer

Absorption

Rapid but variable.

Toxicity

Oral LD50 in mice is over 5011 mg/kg. Doses of 2300 mg/kg in the rat and 2400 mg/kg in the mouse produced ataxia, convulsions, labored respiration and frequently death. No case of overdosage has been reported in humans. Limited data indicate that succimer is dialyzable.

Description

Succimer is a newly available oral chelator of lead and other heavy metals. The compound is indicated for the treatment of lead poisoning in children. Succimer does not bind iron, calcium or magnesium and preferentially binds lead, mercury and arsenic over copper or zinc. The metal-bound succimer is excreted in the urine. The drug may also be effective in adults.

Chemical properties

white or off-white powder

Originator

Johnson and Johnson (J&J) (U.S.A.)

The Uses of Succimer

chelating agent, antihypertensive

The Uses of Succimer

meso-2,3-Dimercaptosuccinic Acid is used as a chelating agent and masking agent for cadmium in EDTA titration of zinc.

The Uses of Succimer

chelating agent, treatment of lead poisoning

The Uses of Succimer

A water-soluble chelating agent.

Indications

For the treatment of lead poisoning in pediatric patients with blood lead levels above 45 μg/dL. May also be used to treat mercury or arsenic poisoning.

Background

A mercaptodicarboxylic acid used as an antidote to heavy metal poisoning because it forms strong chelates with them.

What are the applications of Application

DMSA (Meso-2,3-dimercaptosuccinic acid) is a water-soluble chelating agent

Definition

ChEBI: A sulfur-containing carboxylic acid that is succinic acid bearing two mercapto substituents at positions 2 and 3. A lead chelator used as an antedote to lead poisoning.

Preparation

Isolate the solid complexes of trivalent lanthanide complexes with meso-2,3-Dimercaptosuccinic Acid, furan-2-carboxylic acid, meso-2,3-dimercaptosuccinic acid and sarcosine from the mixture of equimolar solutions of metal nitrates and ligands. Adjust the pH of the mixture to 7 by adding dilute solution of KOH. Reflux the mixture in ethanol (15-20 ml) for 3-4 hours on a steam bath. The clear solution gives a solid mass on cooling, filter through G4 glass crucible and wash several times with the mixture of doubly distilled water and alcohol. Recrystallise it to obtain pure crystal and dry at 60 ?? -70 ??C [1].

brand name

Chemet (Ovation).

Pharmaceutical Applications

Dimercaptosuccinic acid (DMSA) is a modification of BAL containing two thiol groups, which are responsible for the unpleasant smell, and two carboxylic acid groups. DMSA is also known under the name Succimer. It chemical name is meso-2,3-dimercaptosuccinic acid and the chemical formula is HO₂CCH(SH)CH(SH)CO₂H. There are two diastereomeric forms, meso and the chiral DL forms, with the meso isomer being used as chelating agent.
DMSA was developed in the 1960s and replaced BAL and edetate in some countries for the treatment of lead, arsenic and mercury poisoning. Furthermore, the dimethylester modification of DMSA has been successfully used for the treatment of heavy-metal poisoning.

Pharmaceutical Applications

The unlicensed drug Succimer (DMSA, meso-2,3-dimercaptosuccinic acid) may be valuable in the treatment of most forms of heavy-metal poisoning including lead, arsenic and mercury. These and other chelating agents such as unithiol (DMPS, 2,3-dimercapto-1-propanesulfonic acid) and α-lipoic acid (ALA) are also used in alternative medicine, which has led to much criticism and discussion. So far, no medical study has proven the effectiveness of chelation therapy for any clinical application other than heavy-metal poisoning.

Pharmacokinetics

Succimer is an orally active, heavy metal chelating agent. It forms water soluble chelates and, consequently, increases the urinary excretion of lead. Succimer is not to be used for prophylaxis of lead poisoning in a lead-containing environment. In addition, the use of succimer should always be accompanied by identification and removal of the source of the lead exposure.

Veterinary Drugs and Treatments

In veterinary medicine, succimer may be useful for the oral treatment of lead poisoning in small animals (including birds). Potentially, it also may be of benefit for the treatment of other toxic heavy metals such as arsenic or mercury, but more research must be done before this can be recommended.

Metabolism

Chemical analysis of succimer and its metabolites (primarily mixed disulfides of L-cysteine) in the urine showed that succimer was rapidly and extensively metabolized however the specific site of biotransformation is not known.

Purification Methods

Purify the acid by dissolving it in NaOH and precipitating with dilute HCl, drying and recrystallising from MeOH. IR has at 2544 (SH) and max 1689 (CO2H) cm-1 . The bis-S-acetyl derivative has m 183-185o (from EtOAc or Me2CO), and its Me ester has m 119-120o (from pet ether) [Gerecke et al. Helv Chim Acta 44 957 1961, Owen & Sultanbawa J Chem Soc 3112 1949]. [Beilstein 3 III 1033.]