title: Mechanism of action of anticoagulants: correlation between the inhibition of prothrombin synthesis and the regeneration of vitamin K1 from vitamin K1 epoxide.
abstract: It has been proposed that coumarin and indandione anticoagulants inhibit clotting protein synthesis by preventing the regeneration of vitamin K1 from its 2,3-epoxide metabolic. To test this hypothesis, the effects of nine coumarin and indandiones on prothrombin synthesis and the conversion of vitamin K1 epoxide to vitamin K1 were measured. There was a good correlation between the inhibition of prothrombin synthesis and the epoxide-K1 conversion both in vivo and in vitro. Diphenadione (2-diphenyl acetyl-1,3-indandione) caused a delayed inhibition of prothrombin synthesis which correlated with a delayed inhibition of the epoxide-K1 conversion in vivo. These results provide strong evidence for the proposed mechanism of action of coumarin and indandione anticoagulants.
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D003374:Coumarins / Q000494:pharmacology; D005260:Female; D008297:Male; D010630:Phenindione / Q000494:pharmacology; D011516:Prothrombin / Q000096:biosynthesis*; D051381:Rats; D014812:Vitamin K / Q000378:metabolism*
chemical_list: D000925:Anticoagulants; D003374:Coumarins; D014812:Vitamin K; D010630:Phenindione; D011516:Prothrombin