Not to be confused with Coumadin or coumarin.
Dicoumarol
|
Systematic (IUPAC) name |
3,3'-methylenebis(4-hydroxy-2H-chromen-2-one) |
Clinical data |
MedlinePlus |
a605015 |
Pregnancy cat. |
? |
Legal status |
℞-only (US) |
Pharmacokinetic data |
Protein binding |
plasmatic proteins |
Metabolism |
hepatic |
Excretion |
faeces, urine |
Identifiers |
CAS number |
66-76-2 Y |
ATC code |
B01AA01 |
PubChem |
CID 653 |
DrugBank |
DB00266 |
ChemSpider |
10183330 Y |
UNII |
7QID3E7BG7 Y |
KEGG |
D03798 Y |
ChEBI |
CHEBI:4513 Y |
ChEMBL |
CHEMBL1466 Y |
NIAID ChemDB |
016070 |
Chemical data |
Formula |
C19H12O6 |
Mol. mass |
336.295 g/mol |
SMILES
- c1ccc2c(c1)c(c(c(=O)o2)Cc3c(c4ccccc4oc3=O)O)O
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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
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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]
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 Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.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.
Contents
- 1 Mechanism of action
- 2 Uses
- 3 References
- 4 External links
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.
References[edit]
- ^ Nicole Kresge, Robert D. Simoni and Robert L. Hill (2005-02-25). "Sweet clover disease and warfarin review". Jbc.org. Retrieved 2012-09-26.
- 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]
Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)
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Anticoagulants |
Vitamin K antagonists
(inhibit II, VII, IX, X)
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- coumarins: Acenocoumarol
- Coumatetralyl
- Dicoumarol
- Ethyl biscoumacetate
- Phenprocoumon
- Warfarin#
- 1,3-Indandiones: Clorindione
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- other: Tioclomarol
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Factor Xa inhibitors
(with some II inhibition)
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Heparin group/
glycosaminoglycans/
(bind antithrombin)
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Non-medicinal |
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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cell/phys (coag, heme, immu, gran), csfs
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rbmg/mogr/tumr/hist, sysi/epon, btst
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drug (B1/2/3+5+6), btst, trns
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Types of coumarins
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Aglycones |
- Aesculetin
- Ferujol
- Umbelliferone
O-Methylated
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- Fraxetin
- Herniarin (7-O-Methylumbelliferone)
- Osthol
- Scopoletin (6-Methoxyumbelliferone)
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glycosides |
- Aesculin (Esculetin 6-O-glucoside)
- Fraxin (Fraxetin glucoside)
- Skimmin (Umbelliferone 7-O-glucoside)
- Scopolin
- Umbelliferone 7-apiosylglucoside
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derivatives |
Furanocoumarins
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Aglycones
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- Angelicin
- Marmesin
- Psoralen
- Vaginol
- Xanthotoxol (8-Hydroxypsoralen)
O-Methylated
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- Bergapten (5-methoxypsoralen)
- Isopimpinellin (5,8-Dimethoxypsoralene)
- Methoxsalen (8-Methoxypsoralen)
- Trioxsalen (2,5,9-Trimethylpsoralen)
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Furanocoumarin glycosides
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- Apterin (vaginol glucoside)
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Meroterpene furanocoumarin ether
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- Auraptene
- Bergamottin
- Imperatorin
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Oligomers |
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Synthetic |
- Acenocoumarol
- Coumatetralyl
- Ensaculin
- Ethyl biscoumacetate
- 4-Hydroxycoumarins
- Hymecromone
- Phenprocoumon
- Warfarin
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