Dicoumarol

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To be distinguished from Coumadin or coumarin.
Dicoumarol
Dicumarol.svg
Systematic (IUPAC) name
3,3'-methylenebis(4-hydroxy-2H-chromen-2-one)
Clinical data
MedlinePlus a605015
Legal status -only (US) Withdrawn from us market
Pharmacokinetic data
Protein binding plasmatic proteins
Metabolism hepatic
Excretion faeces, urine
Identifiers
CAS number 66-76-2 YesY
ATC code B01AA01
PubChem CID 653
DrugBank DB00266
ChemSpider 10183330 YesY
UNII 7QID3E7BG7 YesY
KEGG D03798 YesY
ChEBI CHEBI:4513 YesY
ChEMBL CHEMBL1466 YesY
NIAID ChemDB 016070
Chemical data
Formula C19H12O6 
Mol. mass 336.295 g/mol
 N (what is this?)  (verify)

Dicoumarol (INN) or dicumarol (USAN) is a naturally occurring anticoagulant that functions as a functional vitamin K depleter (similar to warfarin, a drug that dicoumarol inspired). It is also used in biochemical experiments as an inhibitor of reductases.

Dicoumarol is a natural chemical substance of combined plant and fungal origin. It is a derivative of coumarin, a bitter tasting but sweet-smelling substance made by plants that does not itself affect coagulation, but which is (classically) transformed in mouldy feeds or silages by a number of species of fungi, into active dicoumarol. Dicoumarol does affect coagulation, and was discovered in mouldy wet sweet-clover hay, as the cause of a naturally occurring bleeding disease in cattle.[1] See warfarin for a more detailed discovery history.

Identified in 1940, dicoumarol became the prototype of the 4-hydroxycoumarin derivative anticoagulant drug class. Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.

It is given orally, and it acts within two days.

Mechanism of action[edit]

Like all 4-hydroxycoumarin drugs it is a competitive inhibitor of vitamin K epoxide reductase, an enzyme that recycles vitamin K, thus causing depletion of active vitamin K in blood. This prevents the formation of the active form of prothrombin and several other coagulant enzymes.

These compounds are not direct antagonists (in the pharmaceutical sense) of vitamin K itself, but rather act to deplete reduced vitamin K in tissues. For this reason vitamin K antagonizes their effect (rather than the reverse), and this has led to the loose terminology of vitamin K antagonism.

Administration of vitamin K is therefore the antidote for dicoumarol toxicity. The action and toxicity of the drug and the antidote effectiveness are measured with the prothrombin time (PT) blood test.

Uses[edit]

Dicoumarol was used along with heparin, for the treatment of deep venous thrombosis. Unlike heparin, this class of drugs may be used for months or years.

Poisoning[edit]

Overdose results in serious, sometimes fatal uncontrolled hemorrhage. [2]

References[edit]

  1. ^ Nicole Kresge, Robert D. Simoni and Robert L. Hill (2005-02-25). "Sweet clover disease and warfarin review". Jbc.org. Retrieved 2012-09-26. 
  2. ^ Duff, I. F.; Shull, W. H. (1949). "Fatal Hemorrhage in Dicumarol® Poisoning". Journal of the American Medical Association 139 (12): 762–6. doi:10.1001/jama.1949.02900290008003. PMID 18112552.  edit
  • Cullen J, Hinkhouse M, Grady M, Gaut A, Liu J, Zhang Y, Weydert C, Domann F, Oberley L (2003). "Dicumarol inhibition of NADPH: quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism.". Cancer Res 63 (17): 5513–20. PMID 14500388. 
  • Mironov A, Colanzi A, Polishchuk R, Beznoussenko G, Mironov A, Fusella A, Di Tullio G, Silletta M, Corda D, De Matteis M, Luini A (2004). "Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport.". Eur J Cell Biol 83 (6): 263–79. doi:10.1078/0171-9335-00377. PMID 15511084. 
  • Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz L (2005). "Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication.". Arch Biochem Biophys 434 (2): 241–7. doi:10.1016/j.abb.2004.11.002. PMID 15639223. 
  • Thanos C, Liu Z, Reineke J, Edwards E, Mathiowitz E (2003). "Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride.". Pharm Res 20 (7): 1093–100. doi:10.1023/A:1024474609667. PMID 12880296. ]

External links[edit]