Dimercaprol

Identification

Name
Dimercaprol
Accession Number
DB06782
Type
Small Molecule
Groups
Approved
Description

Dimercaprol is a traditional chelating agent developed by British biochemists at Oxford University during World War II. It was developed as an experimental antidote against the arsenic-based poison gas Lewisite. It has been used clinically since 1949 in arsenic, cadmium and mercury poisoning. In addition, it has in the past been used for the treatment of Wilson's disease, a genetic disorder in which the body tends to retain copper. Dimercaprol is a potentially toxic drug, and its use may be accompanied by multiple side effects.

Structure
Thumb
Synonyms
  • 1,2-Dimercapto-3-propanol
  • 1,2-Dithioglycerol
  • 2,3-Dimercapro
  • 2,3-Dimercapto-1-propanol
  • 2,3-Dimercaptol-1-propanol
  • 2,3-Dimercaptopropanol
  • 2,3-Dithiopropanol
  • 2,3-Mercaptopropan-1-ol
  • 2,3-Mercaptopropanol
  • 3-Hydroxy-1,2-propanedithiol
  • alpha,beta-Dithioglycerol
  • BAL
  • British Anti-Lewisite
  • British antilewisite
  • Dimercaprolum
  • Dimercaptopropanol
  • Dithioglycerine
  • Dithioglycerol
  • Sulfactin
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
BalInjection100 mg/mLIntramuscularAkorn2012-05-01Not applicableUs
Bal In Oil 3ml Ampules/10Solution100 mgIntramuscularTaylor Pharmaceuticals1995-12-31Not applicableCanada
International/Other Brands
Bal In Oil Injection (Taylor Pharmaceuticals) / Dimaval (Heyl) / Dimercaprol (Akorn) / TechneScan DMSA (Mallinckrodt)
Categories
UNII
0CPP32S55X
CAS number
59-52-9
Weight
Average: 124.225
Monoisotopic: 124.001656258
Chemical Formula
C3H8OS2
InChI Key
WQABCVAJNWAXTE-UHFFFAOYSA-N
InChI
InChI=1S/C3H8OS2/c4-1-3(6)2-5/h3-6H,1-2H2
IUPAC Name
2,3-disulfanylpropan-1-ol
SMILES
OCC(S)CS

Pharmacology

Indication

For the treatment of arsenic, gold and mercury poisoning. Indicated in acute lead poisoning when used concomitantly with edetate calcium disodium (DB00974).

Structured Indications
Pharmacodynamics

Due to its oily nature, dimercaprol is not absorbed orally and its administration requires deep intra-muscular injection that is extremely painful and allergenic. It was found to mobilize and relocate lead to the brain, increasing its neurotoxic effects. Although treatment with dimercaprol increases the excretion of cadmium, there is a concomitant increase in renal cadmium concentration, so its use should be avoided in cases of cadmium toxicity.

Mechanism of action

The sulfhydryl groups of dimercaprol form complexes with certain heavy metals thus preventing or reversing the metallic binding of sulfhydryl-containing enzymes. The complex is excreted in the urine.

TargetActionsOrganism
AArsenic
chelator
Human
ACadmium
chelator
Human
AMercury
chelator
Human
UAmyloid beta A4 proteinNot AvailableHuman
Absorption

After intra-muscular injection.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Urine.

Half life

The drug has a short half life.

Clearance
Not Available
Toxicity

The intramuscular LD50 in rats is approximately 105 mg/kg; intraperitoneally 140 mg/kg. The intraperitoneal LD80 in mice is approximately 125 mg/kg. Dimercaprol has been shown in animal experiments to increase brain deposition of arsenite, organic mercury compounds and increase the toxicity of cadmium and lead. Dimercaprol has been shown to induce seizure in animal studies and also is nephrotoxic.

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
Technetium Tc-99m oxidronateDimercaprol can cause a decrease in the absorption of Technetium Tc-99m oxidronate resulting in a reduced serum concentration and potentially a decrease in efficacy.Approved
Food Interactions
Not Available

References

Synthesis Reference

Peppel, W.J. and Signaigo, F.K.; U.S. Patent 2,402,665; June 25,1946; assigned to E.I. du Pont de Nemwrs & Company.

General References
  1. Walshe JM: The conquest of Wilson's disease. Brain. 2009 Aug;132(Pt 8):2289-95. doi: 10.1093/brain/awp149. Epub 2009 Jul 13. [PubMed:19596747]
  2. Boscolo M, Antonucci S, Volpe AR, Carmignani M, Di Gioacchino M: Acute mercury intoxication and use of chelating agents. J Biol Regul Homeost Agents. 2009 Oct-Dec;23(4):217-23. [PubMed:20003760]
  3. Flora SJ, Pachauri V: Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Jul;7(7):2745-88. doi: 10.3390/ijerph7072745. Epub 2010 Jun 28. [PubMed:20717537]
  4. Andersen O: Chemical and biological considerations in the treatment of metal intoxications by chelating agents. Mini Rev Med Chem. 2004 Jan;4(1):11-21. [PubMed:14754439]
External Links
Human Metabolome Database
HMDB15677
KEGG Drug
D00167
KEGG Compound
C02924
PubChem Compound
3080
PubChem Substance
99443293
ChemSpider
2971
ChEBI
64198
ChEMBL
CHEMBL1597
PharmGKB
PA165958406
Wikipedia
Dimercaprol
ATC Codes
V03AB09 — Dimercaprol
AHFS Codes
  • 64:00.00 — Heavy Metal Antagonists
FDA label
Download (111 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InjectionIntramuscular100 mg/mL
SolutionIntramuscular100 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)< 25 °CPhysProp
boiling point (°C)140 °C at 4.00E+01 mm HgPhysProp
water solubility8.7E+004 mg/LMERCK INDEX (1996)
pKa8.62 (at 25 °C)SARGEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
Water Solubility2.76 mg/mLALOGPS
logP0.58ALOGPS
logP0.21ChemAxon
logS-1.6ALOGPS
pKa (Strongest Acidic)9.58ChemAxon
pKa (Strongest Basic)-2.8ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count1ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area20.23 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity32.91 m3·mol-1ChemAxon
Polarizability12.88 Å3ChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.922
Blood Brain Barrier+0.7436
Caco-2 permeable-0.5646
P-glycoprotein substrateNon-substrate0.7655
P-glycoprotein inhibitor INon-inhibitor0.9769
P-glycoprotein inhibitor IINon-inhibitor0.9838
Renal organic cation transporterNon-inhibitor0.9355
CYP450 2C9 substrateNon-substrate0.8031
CYP450 2D6 substrateNon-substrate0.8659
CYP450 3A4 substrateNon-substrate0.8388
CYP450 1A2 substrateInhibitor0.8792
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9413
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.9674
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8851
Ames testNon AMES toxic0.837
CarcinogenicityNon-carcinogens0.5788
BiodegradationReady biodegradable0.6332
Rat acute toxicity2.6518 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9667
hERG inhibition (predictor II)Non-inhibitor0.9257
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 alkylthiols. These are organic compounds containing the thiol functional group linked to an alkyl chain.
Kingdom
Organic compounds
Super Class
Organosulfur compounds
Class
Thiols
Sub Class
Alkylthiols
Direct Parent
Alkylthiols
Alternative Parents
Primary alcohols / Hydrocarbon derivatives
Substituents
Alkylthiol / Organic oxygen compound / Hydrocarbon derivative / Primary alcohol / Organooxygen compound / Alcohol / Aliphatic acyclic compound
Molecular Framework
Aliphatic acyclic compounds
External Descriptors
primary alcohol, dithiol (CHEBI:64198) / a small molecule (23-DIMERCAPTOPROPAN-1-OL)

Targets

1. Arsenic
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Chelator
References
  1. Flora SJ, Pachauri V: Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Jul;7(7):2745-88. doi: 10.3390/ijerph7072745. Epub 2010 Jun 28. [PubMed:20717537]
2. Cadmium
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Chelator
References
  1. Flora SJ, Pachauri V: Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Jul;7(7):2745-88. doi: 10.3390/ijerph7072745. Epub 2010 Jun 28. [PubMed:20717537]
Kind
Small molecule
Organism
Human
Pharmacological action
Yes
Actions
Chelator
References
  1. Flora SJ, Pachauri V: Chelation in metal intoxication. Int J Environ Res Public Health. 2010 Jul;7(7):2745-88. doi: 10.3390/ijerph7072745. Epub 2010 Jun 28. [PubMed:20717537]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Transition metal ion binding
Specific Function
Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. Involved in cell mobility and tra...
Gene Name
APP
Uniprot ID
P05067
Uniprot Name
Amyloid beta A4 protein
Molecular Weight
86942.715 Da
References
  1. Venti A, Giordano T, Eder P, Bush AI, Lahiri DK, Greig NH, Rogers JT: The integrated role of desferrioxamine and phenserine targeted to an iron-responsive element in the APP-mRNA 5'-untranslated region. Ann N Y Acad Sci. 2004 Dec;1035:34-48. [PubMed:15681799]

Drug created on September 14, 2010 10:21 / Updated on January 14, 2018 10:04