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Not to be confused with Coumadin or coumarin.
Systematic (IUPAC) name
Clinical data
MedlinePlus a605015
Legal status
Pharmacokinetic data
Protein binding plasmatic proteins
Metabolism hepatic
Excretion faeces, urine
CAS Registry Number 66-76-2 YesY
ATC code B01AA01
PubChem CID: 653
DrugBank DB00266 N
ChemSpider 10183330 YesY
KEGG D03798 YesY
NIAID ChemDB 016070
Chemical data
Formula C19H12O6
Molecular 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 Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.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.


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.

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.


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


Dicoumarol was isolated by Karl Link's laboratory at University of Wisconsin, six years after a farmer had brought a dead cow and a milk can full of uncoagulated blood to an agricultural extension station of the university. The cow had died of internal bleeding after eating moldy sweet clover; an outbreak of such deaths had begun in the 1920s during The Great Depression as farmers could not afford to waste hay that had gone bad.[3] Link's work led to the develop of the rat poison warfarin and then to the anticoagulants still in clinical use today.[3]


  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. 
  3. ^ a b Wardrop D, Keeling D. The story of the discovery of heparin and warfarin. Br J Haematol. 2008 Jun;141(6):757-63. PMID 18355382


  • 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. ]

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