Identification
NameSuccimer
Accession NumberDB00566  (APRD01236)
TypeSmall Molecule
GroupsApproved
Description

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

Structure
Thumb
Synonyms
Dimercaptosuccinic acid
DMSA
meso-2,3-Dimercaptobernsteinsäure
meso-2,3-dimercaptosuccinic acid
meso-dimercaptosuccinic acid
External IDs RO 1-7977
Product Ingredients Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ChemetCapsule100 mg/1OralRecordati Rare Diseases Inc2013-08-21Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
Categories
UNIIDX1U2629QE
CAS number304-55-2
WeightAverage: 182.21
Monoisotopic: 181.970751021
Chemical FormulaC4H6O4S2
InChI KeyACTRVOBWPAIOHC-XIXRPRMCSA-N
InChI
InChI=1S/C4H6O4S2/c5-3(6)1(9)2(10)4(7)8/h1-2,9-10H,(H,5,6)(H,7,8)/t1-,2+
IUPAC Name
(2R,3S)-2,3-disulfanylbutanedioic acid
SMILES
OC(=O)[C@@H](S)[C@@H](S)C(O)=O
Pharmacology
Indication

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.

Structured Indications
Pharmacodynamics

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.

Mechanism of action

Succimer is a heavy metal chelator. It binds with high specificity to ions of lead in the blood to form a water-soluble complex that is subsequently excreted by the kidneys. Succimer can also chelate mercury, cadmium, and arsenic in this manner.

TargetKindPharmacological actionActionsOrganismUniProt ID
LeadSmall moleculeyes
chelator
Humannot applicabledetails
MercurySmall moleculeyes
chelator
Humannot applicabledetails
CadmiumSmall moleculeyes
chelator
Humannot applicabledetails
ArsenicSmall moleculeyes
chelator
Humannot applicabledetails
Related Articles
Absorption

Rapid but variable.

Volume of distributionNot Available
Protein bindingNot Available
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.

Route of elimination

Unabsorbed drug is excreted primarily in feces and absorbed drug is excreted primarily in the urine as metabolites.

Half life

48 hours

ClearanceNot Available
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.

Affected organisms
  • Humans and other mammals
PathwaysNot Available
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions No interactions found.
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  1. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. [PubMed:9630737 ]
  2. Aaseth J, Jacobsen D, Andersen O, Wickstrom E: Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review. Analyst. 1995 Mar;120(3):853-4. [PubMed:7741240 ]
  3. Mann KV, Travers JD: Succimer, an oral lead chelator. Clin Pharm. 1991 Dec;10(12):914-22. [PubMed:1663439 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (60.1 KB)
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentAutism, Early Infantile1
2WithdrawnTreatmentAsperger's Disorder / Autism, Early Infantile / Child Development Disorders, Pervasive1
3CompletedTreatmentLead Exposure1
Not AvailableCompletedTreatmentPoisoning, Lead1
Pharmacoeconomics
Manufacturers
  • Lundbeck inc
  • Ge healthcare
Packagers
Dosage forms
FormRouteStrength
CapsuleOral100 mg/1
Prices
Unit descriptionCostUnit
Dmsa powder15.61USD g
Chemet 100 mg capsule8.6USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point (°C)193 °CPhysProp
logP-0.3Not Available
Predicted Properties
PropertyValueSource
Water Solubility2.43 mg/mLALOGPS
logP0.56ALOGPS
logP0.26ChemAxon
logS-1.9ALOGPS
pKa (Strongest Acidic)3.37ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area74.6 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity38.47 m3·mol-1ChemAxon
Polarizability15.45 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.5415
Blood Brain Barrier+0.7685
Caco-2 permeable-0.7615
P-glycoprotein substrateNon-substrate0.8129
P-glycoprotein inhibitor INon-inhibitor0.9908
P-glycoprotein inhibitor IINon-inhibitor0.9968
Renal organic cation transporterNon-inhibitor0.9721
CYP450 2C9 substrateNon-substrate0.7885
CYP450 2D6 substrateNon-substrate0.9109
CYP450 3A4 substrateNon-substrate0.8136
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorInhibitor0.5135
CYP450 2D6 inhibitorNon-inhibitor0.9474
CYP450 2C19 inhibitorNon-inhibitor0.9566
CYP450 3A4 inhibitorNon-inhibitor0.9118
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9873
Ames testNon AMES toxic0.8945
CarcinogenicityNon-carcinogens0.6495
BiodegradationReady biodegradable0.8332
Rat acute toxicity1.6901 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9932
hERG inhibition (predictor II)Non-inhibitor0.9736
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as thia fatty acids. These are fatty acid derivatives obtained by insertion of a sulfur atom at specific positions in the chain.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentThia fatty acids
Alternative ParentsDicarboxylic acids and derivatives / alpha-Mercaptocarboxylic acids / Alkylthiols / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
SubstituentsThia fatty acid / Dicarboxylic acid or derivatives / 2-mercaptocarboxylic acid / Carboxylic acid / Carboxylic acid derivative / Alkylthiol / Organic oxygen compound / Organic oxide / Hydrocarbon derivative / Organosulfur compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptorsdicarboxylic acid, dithiol, sulfur-containing carboxylic acid (CHEBI:63623 )

Targets

1. Lead
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
References
  1. Bradberry S, Vale A: Dimercaptosuccinic acid (succimer; DMSA) in inorganic lead poisoning. Clin Toxicol (Phila). 2009 Aug;47(7):617-31. doi: 10.1080/15563650903174828. [PubMed:19663612 ]
  2. Gracia RC, Snodgrass WR: Lead toxicity and chelation therapy. Am J Health Syst Pharm. 2007 Jan 1;64(1):45-53. [PubMed:17189579 ]
  3. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. [PubMed:9630737 ]
  4. Jorgensen FM: Succimer: the first approved oral lead chelator. Am Fam Physician. 1993 Dec;48(8):1496-502. [PubMed:8249780 ]
  5. Aaseth J, Jacobsen D, Andersen O, Wickstrom E: Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review. Analyst. 1995 Mar;120(3):853-4. [PubMed:7741240 ]
  6. Blanusa M, Varnai VM, Piasek M, Kostial K: Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771-94. [PubMed:16305472 ]
  7. Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM: Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995 Mar 31;97(1-3):23-38. [PubMed:7716789 ]
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
References
  1. Ozuah PO: Mercury poisoning. Curr Probl Pediatr. 2000 Mar;30(3):91-9. [PubMed:10742922 ]
  2. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. [PubMed:9630737 ]
  3. Aaseth J, Jacobsen D, Andersen O, Wickstrom E: Treatment of mercury and lead poisonings with dimercaptosuccinic acid and sodium dimercaptopropanesulfonate. A review. Analyst. 1995 Mar;120(3):853-4. [PubMed:7741240 ]
  4. Blanusa M, Varnai VM, Piasek M, Kostial K: Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771-94. [PubMed:16305472 ]
  5. Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM: Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995 Mar 31;97(1-3):23-38. [PubMed:7716789 ]
3. Cadmium
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
References
  1. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. [PubMed:9630737 ]
  2. Blanusa M, Varnai VM, Piasek M, Kostial K: Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771-94. [PubMed:16305472 ]
  3. Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM: Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995 Mar 31;97(1-3):23-38. [PubMed:7716789 ]
4. Arsenic
Kind
Small molecule
Organism
Human
Pharmacological action
yes
Actions
chelator
References
  1. Miller AL: Dimercaptosuccinic acid (DMSA), a non-toxic, water-soluble treatment for heavy metal toxicity. Altern Med Rev. 1998 Jun;3(3):199-207. [PubMed:9630737 ]
  2. Blanusa M, Varnai VM, Piasek M, Kostial K: Chelators as antidotes of metal toxicity: therapeutic and experimental aspects. Curr Med Chem. 2005;12(23):2771-94. [PubMed:16305472 ]
  3. Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM: Mobilization of heavy metals by newer, therapeutically useful chelating agents. Toxicology. 1995 Mar 31;97(1-3):23-38. [PubMed:7716789 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:50