[Synthetic anticoagulant].
Anticoagulant as well as anti-platelet drugs are important medicines for the prophylaxis in various kinds of thrombotic diseases. However, the conventional anticoagulant drugs, heparin and coumarin congeners, have some disadvantages and limitations in clinical usage. Recently newly anticoagulants, both synthetic and recombinant, have been developing. They include synthetic thrombin inhibitor, recombinant hirudin, protein C and thrombomodulin. Here we reviewed synthetic thrombin inhibitor, Argipidine (MD805) in clinical trial and investigated its effect on thrombin catalyzed protein C activation on endothelial cells. Argipidine inhibited the protein C activating activity of thrombin on endothelium in a dose response manner. Next we examined the effect of Argipidine on thrombin-induced endothelin release from cultured endothelial cells. The augmentation of endothelin release from endothelial cells by thrombin was also inhibited by Argipidin. The effect was considered one of the advantage of this drug in the treatment of thrombosis. Recombinant thrombomodulin had potent antithrombotic effect on thrombin-induced acute thromboembolism in mice, suggesting that this may be expectant anticoagulant for DIC or thromboses in human.
Maruyama
I
I
Third Department of Internal Medicine, Kagoshima University School of Medicine, Japan.
D000818:Animals; D000991:Antithrombins; D001120:Arginine / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D006801:Humans; D051379:Mice; D010875:Pipecolic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D011486:Protein C / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000494:pharmacology; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy
D000991:Antithrombins; D016232:Endothelins; D010875:Pipecolic Acids; D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin; D011994:Recombinant Proteins; D013449:Sulfonamides; D001120:Arginine; C031942:argatroban