Dicoumarol

Dicoumarol

Clinical data
MedlinePlus	a605015
ATC code	B01AA01 (WHO)
Legal status
Legal status	US: Template:Infobox drug/non-ref-space
Pharmacokinetic data
Protein binding	plasmatic proteins
Metabolism	hepatic
Excretion	faeces, urine
Identifiers
IUPAC name 3,3'-Methylenebis(4-hydroxy-2H-chromen-2-one)
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PubChem SID	Template:Infobox drug/formatPubChemSID Template:Infobox drug/formatPubChemSID
IUPHAR/BPS	Template:Infobox drug/formatIUPHARBPS Template:Infobox drug/formatIUPHARBPS
DrugBank	Template:Infobox drug/formatDrugBank Template:Infobox drug/formatDrugBank
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UNII	Template:Infobox drug/formatUNII Template:Infobox drug/formatUNII
KEGG	Template:Infobox drug/formatKEGG Template:Infobox drug/formatKEGG
ChEBI	Template:Infobox drug/formatChEBI Template:Infobox drug/formatChEBI
ChEMBL	Template:Infobox drug/formatChEMBL Template:Infobox drug/formatChEMBL
NIAID ChemDB	Template:Infobox drug/formatChemDBNIAID Template:Infobox drug/formatChemDBNIAID
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CompTox Dashboard (EPA)	Template:Infobox drug/formatCompTox Template:Infobox drug/formatCompTox
Chemical and physical data
Formula	C19H12O6
Molar mass	336.299 g·mol−1
3D model (JSmol)	Template:Infobox drug/formatJmol Template:Infobox drug/formatJmol
SMILES O=C1Oc2ccccc2C(O)=C1CC3=C(O)c4ccccc4OC3=O
InChI InChI=1S/C19H12O6/c20-16-10-5-1-3-7-14(10)24-18(22)12(16)9-13-17(21)11-6-2-4-8-15(11)25-19(13)23/h1-8,20-21H,9H2 Y Key:DOBMPNYZJYQDGZ-UHFFFAOYSA-N Y
Data page
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Dicoumarol (INN) or dicumarol (USAN) is a naturally occurring anticoagulant drug that depletes stores of vitamin K (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. See warfarin for a more detailed discovery history.

Identified in 1940, dicoumarol became the prototype of the 4-hydroxycoumarin 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.

Uses

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

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 antagonists of Vitamin K directly—as they are in pharmaceutical uses—but rather promote depletion of vitamin K in bodily tissues allowing vitamin K's mechanism of action as a potent medication for dicoumarol toxicity. The mechanism of action of Vitamin K along with the toxicity of dicoumarol are measured with the prothrombin time (PT) blood test.

Poisoning

Overdose results in serious, sometimes fatal uncontrolled hemorrhage.

History

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. Link's work led to the development of the rat poison warfarin and then to the anticoagulants still in clinical use today.

See also

• Ethyl biscoumacetate

Further reading

• Cullen JJ, Hinkhouse MM, Grady M, Gaut AW, Liu J, Zhang YP, et al. (September 2003). "Dicumarol inhibition of NADPH:quinone oxidoreductase induces growth inhibition of pancreatic cancer via a superoxide-mediated mechanism". Cancer Research. 63 (17): 5513–5520. PMID 14500388.
• Mironov AA, Colanzi A, Polishchuk RS, Beznoussenko GV, Mironov AA, Fusella A, et al. (July 2004). "Dicumarol, an inhibitor of ADP-ribosylation of CtBP3/BARS, fragments golgi non-compact tubular zones and inhibits intra-golgi transport". European Journal of Cell Biology. 83 (6): 263–279. doi:10.1078/0171-9335-00377. PMID 15511084.
• Abdelmohsen K, Stuhlmann D, Daubrawa F, Klotz LO (February 2005). "Dicumarol is a potent reversible inhibitor of gap junctional intercellular communication". Archives of Biochemistry and Biophysics. 434 (2): 241–247. doi:10.1016/j.abb.2004.11.002. PMID 15639223.
• Thanos CG, Liu Z, Reineke J, Edwards E, Mathiowitz E (July 2003). "Improving relative bioavailability of dicumarol by reducing particle size and adding the adhesive poly(fumaric-co-sebacic) anhydride". Pharmaceutical Research. 20 (7): 1093–1100. doi:10.1023/A:1024474609667. PMID 12880296. S2CID 448086.]

External links

• Diseases Database (DDB): 30166