dicumarol

ジクマロール 　

WordNet

1. an anticoagulant drug that has now been largely replaced by warfarin (同)dicoumarol

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/12/25 12:16:52」(JST)

wiki en

[Wiki en表示]

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
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
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.

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 Dicoumarol itself, for a short time, was employed as a medicinal anticoagulant drug, but since the mid-1950s has been replaced by its simpler derivative warfarin, and other 4-hydroxycoumarin drugs.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

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

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

• 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

• DDB 30166

English Journal

• Targeting PSG1 to enhance chemotherapeutic efficacy: new application for anti-coagulant the dicumarol.

• He DX1, Gu F2, Wu J3, Gu XT4, Lu CX4, Mao AQ4, Zhang GY1, Ding ZY1, Wang JK3, Hao JJ5, Fu L6, Ma X7.
• Clinical science (London, England : 1979).Clin Sci (Lond).2016 Dec 1;130(24):2267-2276. Epub 2016 Sep 21.
• Chemotherapeutic response is critical for the successful treatment and good prognosis in cancer patients. In this study, we analysed the gene expression profiles of preoperative samples from oestrogen receptor (ER)-negative breast cancer patients with different responses to taxane-anthracycline-base
• PMID 27653744

• Bromate Reduction by Rhodococcus sp. Br-6 in the Presence of Multiple Redox Mediators.

• Tamai N1, Ishii T1, Sato Y1, Fujiya H1, Muramatsu Y2, Okabe N2, Amachi S1.
• Environmental science & technology.Environ Sci Technol.2016 Oct 4;50(19):10527-10534. Epub 2016 Sep 23.
• A bromate (BrO3-)-reducing bacterium, designated Rhodococcus sp. strain Br-6, was isolated from soil. The strain reduced 250 μM bromate completely within 4 days under growth conditions transitioning from aerobic to anaerobic conditions, while no reduction was observed under aerobic and anaerobic gr
• PMID 27612520

• Cryptotanshinone Induces Pro-death Autophagy through JNK Signaling Mediated by Reactive Oxygen Species Generation in Lung Cancer Cells.

• Hao W, Zhang X, Zhao W, Zhu H, Liu ZY, Lu J, Chen X1.
• Anti-cancer agents in medicinal chemistry.Anticancer Agents Med Chem.2016;16(5):593-600.
• Cryptotanshinone (CTS), a natural product isolated from Salvia miltiorrhiza Bunge, demonstrates anticancer effect. Previous reports showed that CTS induced caspase-independent cell death. Here, we reported that CTS induced pro-death autophagy in human lung cancer cells. CTS inhibited the proliferati
• PMID 26343144

Japanese Journal

• Evaluation of selective competitive binding of basic drugs to α1-acid glycoprotein variants

• Ishizaki Junko,Fukaishi Akiko,Fukuwa Chie,Yamazaki Satoko,Tabata Mayu,Ishida Takuya,Suga Yukio,Arai Kunizo,Yokogawa Koichi,Miyamoto Kenichi
• Biological and Pharmaceutical Bulletin 33(1), 95-99, 2010-01-00
• … The selective binding to these variants was evaluated by measuring the displacement ratio of dicumarol bound to the F1S variant or that of acridine orange bound to the A variant, using circular dichroism spectroscopy. …
• NAID 120001939470

• Evaluation of Selective Competitive Binding of Basic Drugs to .ALPHA.1-Acid Glycoprotein Variants

• Ishizaki Junko,Fukaishi Akiko,Fukuwa Chie,Yamazaki Satoko,Tabata Mayu,Ishida Takuya,Suga Yukio,Arai Kunizo,Yokogawa Koichi,Miyamoto Ken-ichi
• Biological and Pharmaceutical Bulletin 33(1), 95-99, 2010
• … The selective binding to these variants was evaluated by measuring the displacement ratio of dicumarol bound to the F1S variant or that of acridine orange bound to the A variant, using circular dichroism spectroscopy. …
• NAID 130000140199

• Involvement of carbonyl reductase in superoxide formation through redox cycling of adrenochrome and 9,10-phenanthrenequinone in pig heart

• Oginuma Michiko,Shimada Hideaki,Imamura Yorishige,オギヌマ ミチコ,シマダ ヒデアキ,イマムラ ヨリシゲ,荻沼 道子,島田 秀昭,今村 順茂
• Chemico-Biological Interactions 155(3), 148-154, 2005-08-15
• … Dicumarol, a potent inhibitor of DT-diaphorase, had little effect on the time course of NADPH oxidation during the reduction of PQ. …
• NAID 120005254874

Related Links

• Dicumarol Advanced Patient Information - Drugs.com

Detailed drug Information for Dicumarol. Includes common brand names, drug descriptions, warnings, side effects and dosing information. ... Abdominal or stomach pain or swelling; back pain or backaches; black, tarry ...

• dicumarol oral : Uses, Side Effects, Interactions, Pictures ...

Find patient medical information for dicumarol oral on WebMD including its uses, side effects and safety, interactions, pictures, warnings and user ratings. ... Selected from data included with permission and copyrighted by First ...

Related Pictures

---

★リンクテーブル★

リンク元

「ジクマロール」

「ジクマロール」

　　[★]

英

dicumarol、dicoumarol

同

ビスヒドロキシクマリン bishydroxycoumarin, 4-hydroxydicoumarin