Identification | |
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Name | Phenindione |
Accession Number | DB00498 (APRD00166) |
Type | small molecule |
Description | An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234) |
Structure |
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Categories (*) | |
Molecular Weight | 222.2387 |
Groups | approved |
Monoisotopic Weight | 222.068079564 |
Pharmacology | |
Indication | For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis. |
Mechanism of action | Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. |
Absorption | Absorbed slowly from the gastrointestinal tract. |
Protein binding | 88% |
Biotransformation | Hepatic. |
Route of elimination | Not Available |
Toxicity | Oral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg. |
Affected organisms |
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Interactions | |
Drug Interactions | Not Available |
Food Interactions | Not Available |
Vitamin K epoxide reductase complex subunit 1 | |
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Name | Vitamin K epoxide reductase complex subunit 1 |
Gene Name | VKORC1 |
Pharmacological action | yes |
Actions | inhibitor |
References |
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DTHybrid score | 0.471 |