MECHANISM OF ACTION OF ANTICOAGULANTS - CORRELATION BETWEEN INHIBITION OF PROTHROMBIN SYNTHESIS AND REGENERATION OF VITAMIN-K1 FROM VITAMIN-K1 EPOXIDE

  • 1 January 1977
    • journal article
    • research article
    • Vol. 201  (3) , 541-546
Abstract
Coumarin and indandione anticoagulants appear to inhibit clotting protein synthesis by preventing the regeneration of vitamin K1 from its 2,3-epoxide metabolite. To test this hypothesis, the effects of 9 coumarins 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 [rats]. 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. Strong evidence is presented for the proposed mechanism of action of coumarin and indandione anticoagulants.

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