Comparative Studies on Thrombin Inhibitors in Experimental Microthrombosis

Summary

The influence of thrombin inhibitors, which differ both in their chemical structure and type of inhibition on thrombin-induced microthrombosis was studied in rat lungs. The antithrombotically effective doses and blood levels of the compounds correlated with their kinetic constants for inhibition of thrombin. In preventing microthrombosis, some of the synthetic inhibitors tested surpassed the effectiveness of heparin and approached that of the naturally occurring inhibitor hirudin.

Keywords

Thrombin inhibitors - Experimental DIC - Prevention of microthrombosis in lungs

• References

• 1 Markwardt F. Pharmacological control of blood coagulation by snythetic, low-molecular-weight inhibitors of clotting enzymes. A new concept of anticoagulants. Trends Pharmacol Sci 1980; 01: 153-157
• 2 Markwardt F. Approaches for designing synthetic, low molecular weight inhibitors of clotting enzymes. Folia Haematol (Leipz.) 1982; 109: 07-15
• 3 Markwardt F, Nowak G, Hoffmann J. The influence of drugs on disseminated intravascular coagulation (DIC). Effects of naturally occurring and synthetic thrombin inhibitors. Thromb Res 1977; 11: 275-283
• 4 Hauptmann J, Kaiser B, Markwardt F, Nowak G. Anticoagulant and antithrombotic action of novel specific inhibitors of thrombin. Thromb Haemostas 1980; 43: 118-123
• 5 Walsmann P. Über die Reinigung von Thrombinpräparaten. Phar-mazie 1968; 23: 401-402
• 6 Wagner G, Horn H, Richter P, Vieweg H, Lischke I, Kazmirowski H-G. Synthese antiproteolytisch wirksamer Nα-arylsulfonylierter Amidinophenylalaninamide. Pharmazie 1981; 36: 597-603
• 7 Wagner G, Voigt B, Vieweg H, Markwardt F, Stiirzebecher J. Verfahren zur Herstellung von Nα-aryl-bzw. Nα-heteroarylsulfonyl-aminoacylierten Amidino-phenylalaninamiden. DDR-Wirtschaftspa-tent 155 954, 3. 2. 1981
• 8 Markwardt F. Hirudin as an inhibitor of thrombin. In: Methods in Enzymology Proteolytic Enzymes. Perlmann GE, Lorand L. (eds). Academic Press; New York: 1970. 19. 924-932
• 9 Stürzebecher J, Markwardt F, Voigt B, Wagner G, Walsmann P. Cyclic amides of Nα-arylsulfonylaminoacylated 4-amidinophenyl-alanine – tight binding inhibitors of thrombin. Thromb Res. 1983 in press.
• 10 Kettner C, Shaw E. D-Phe-Pro-ArgCH₂Cl – a selective affinity label for thrombin. Throm Res 1979; 14: 969-973
• 11 Koth W, Nowak G, Markwardt F. Monitoring of microthrombosis in experimental animals by continuous recording of ¹²⁵I-fibrin deposits and ⁵¹Cr-labelled platelets in the lungs. Acta Biol Med Ger 1980; 39: 157-162