Contents

Dicoumarol

Dicoumarol

Clinical data
MedlinePlus	a605015
ATC code	B01AA01 (WHO)
Legal status
Legal status	US: Withdrawn from market
Pharmacokinetic data
Protein binding	plasmatic proteins
Metabolism	hepatic
Excretion	faeces, urine
Identifiers
IUPAC name 3,3'-Methylenebis(4-hydroxy-2H-chromen-2-one)
CAS Number	66-76-2 Y
PubChem CID	653
IUPHAR/BPS	6808
DrugBank	DB00266 N
ChemSpider	10183330 Y
UNII	7QID3E7BG7
KEGG	D03798 Y
ChEBI	CHEBI:4513 Y
ChEMBL	ChEMBL1466 Y
NIAID ChemDB	016070
CompTox Dashboard (EPA)	DTXSID8021729
ECHA InfoCard	100.000.575
Chemical and physical data
Formula	C19H12O6
Molar mass	336.299 g·mol−1
3D model (JSmol)	Interactive image
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
NY (what is this?)  (verify)

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.^[1] 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 Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.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[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.

Mechanism of action[edit]

Like all 4-hydroxycoumarin drugs it is a competitive inhibitorofvitamin 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[edit]

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

History[edit]

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 development of the rat poison warfarin and then to the anticoagulants still in clinical use today.^[3]

See also[edit]

• Ethyl biscoumacetate

References[edit]

Further reading[edit]

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External links[edit]

• Diseases Database (DDB): 30166