Succimer

Identification

Name
Succimer
Accession Number
DB00566  (APRD01236)
Type
Small Molecule
Groups
Approved
Description

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

Structure
Thumb
Synonyms
  • DIM-SA
  • DMS
  • DMS-A
  • DMSA
  • meso-2,3-Dimercaptobernsteinsäure
  • meso-2,3-dimercaptosuccinic acid
  • meso-dimercaptosuccinic acid
External IDs
RO 1-7977
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ChemetCapsule100 mg/1OralLundbeck Inc.1991-01-302013-04-15Us
ChemetCapsule100 mg/1OralRECORDATI RARE DISEASES, INC.2013-08-21Not applicableUs
Categories
UNII
DX1U2629QE
CAS number
304-55-2
Weight
Average: 182.21
Monoisotopic: 181.970751021
Chemical Formula
C4H6O4S2
InChI Key
ACTRVOBWPAIOHC-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.

Associated Conditions
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.

TargetActionsOrganism
ALead
chelator
Human
AMercury
chelator
Human
ACadmium
chelator
Human
AArsenic
chelator
Human
Absorption

Rapid but variable.

Volume of distribution
Not Available
Protein binding
Not 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

Clearance
Not 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
Technetium Tc-99m oxidronateSuccimer may decrease effectiveness of Technetium Tc-99m oxidronate as a diagnostic agent.
Food Interactions
Not Available

References

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
KEGG Drug
D00572
KEGG Compound
C07598
PubChem Compound
2724354
PubChem Substance
46504680
ChemSpider
2006502
BindingDB
50232640
ChEBI
63623
ChEMBL
CHEMBL1201073
PharmGKB
PA451521
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Succimer
MSDS
Download (60.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1, 2CompletedTreatmentAutism, Early Infantile1
2RecruitingTreatmentAcute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome / Acute, secondary Myeloid Leukemia / Chronic Myelogenous Leukemia, BCR-ABL1 Positive / Chronic Myelomonocytic Leukemia / Leukemia Acute Myeloid Leukemia (AML) / Myelodysplastic Syndrome / Myelodysplastic/Myeloproliferative Neoplasms1
2WithdrawnTreatmentAsperger's Disorder / Autism, Early Infantile / Child Development Disorders, Pervasive1
3CompletedTreatmentLead Exposure1
4RecruitingOtherHeart Failure, Unspecified1
Not AvailableCompletedTreatmentPoisoning, Lead1

Pharmacoeconomics

Manufacturers
  • Lundbeck inc
  • Ge healthcare
Packagers
  • GE Healthcare Inc.
  • Lundbeck Inc.
  • Medi-Physics Inc.
  • Medisca Inc.
  • Sanofi-Aventis Inc.
  • Schwarz Pharma Inc.
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.
Patents
Not Available

Properties

State
Solid
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
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Fatty Acyls
Sub Class
Fatty acids and conjugates
Direct Parent
Thia fatty acids
Alternative Parents
Dicarboxylic acids and derivatives / alpha-Mercaptocarboxylic acids / Alkylthiols / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds
Substituents
Thia 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 Framework
Aliphatic acyclic compounds
External Descriptors
dicarboxylic 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 October 01, 2018 12:50