Experimental Studies on the Antithrombotic Action of a Highly Effective Synthetic Thrombin Inhibitor

B Kaiser; F Markwardt

doi:10.1055/s-0038-1661520

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1986; 55(02): 194-196
DOI: 10.1055/s-0038-1661520

Original Article

Schattauer GmbH Stuttgart

Experimental Studies on the Antithrombotic Action of a Highly Effective Synthetic Thrombin Inhibitor

Authors

B Kaiser

The Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Erfurt, GDR
F Markwardt

The Institute of Pharmacology and Toxicology, Medical Academy Erfurt, Erfurt, GDR

Abstract

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Summary

The antithrombotic action of the highly effective synthetic thrombin inhibitor Nα-(2-naphthylsulfonylglycyl)-4-amidino-phenylalanine piperidide was studied in various models of experimental thrombosis in rats. Intravenous infusion of the thrombin inhibitor caused a dose-dependent inhibition or prevention of stasis-induced venous thrombosis, of arterial thrombosis after electrically-induced damage of the vessel wall and of thrombotic occlusion of an extracorporeal arterio-venous shunt.

Key words

Experimental models of thrombosis - Synthetic thrombin inhibitor - Antithrombotic action

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References

References
1 Markwardt F. Pharmacologic control of blood coagulation by synthetic, low molecular weight inhibitors of clotting enzymes. In: Annals of the New York Academy of Sciences Walz DA, McCoy LE. (eds.) pp 757-764 Vol. 370 Contributions to Hemostasis. The New York Academy of Sciences; New York, N. Y: 1981
2 Markwardt F, Wagner G, Stürzebecher J, Walsmann P. Nα-Arylsul-fonyl-ω-(4-amidinophenyl)-a-aminoalkylcarboxylic acid amides -novel selective inhibitors of thrombin. Thromb Res 1980; 17: 425-431
3 Stürzebecher J, Markwardt F, Voigt B, Wagner G, Walsmann P. Cyclic amides of Nα-Arylsulfonylaminoacylated 4-amidino-phenyl-alanine - tight binding inhibitors of thrombin. Thromb Res 1983; 29: 635-642
4 Wagner G, Voigt B, Vie weg H, Markwardt F, Stürzebecher J. Verfahren zur Herstellung von Nα-aryl- bzw. Na-heteroarylsulfonyl-aminoacylierten Amidinophenylalaninamiden. DDR-Wirtschaftspa-tent 155954, 3.2 1981
5 Wessler S, Reimer SM, Sheps MC. Biologie assay of a thrombosis-inducing activity in human serum. J Appl Physiol 1959; 14: 943-946
6 Hladovec J. Experimental arterial thrombosis in rats with continuous registration. Thrombos Diathes Haemorrh 1971; 26: 407-410
7 Ashida S, Sakuma K, Abiko Y. Antithrombotic effects of ticlopidine, acetylsalicylic acid and dipyridamole in vascular shunt model in rats. Thromb Res 1980; 17: 663-671
8 Kaiser B, Hauptmann J, Weiß A, Markwardt F. Pharmacological characterization of a new highly effective synthetic thrombin inhibitor. Biomed Biochim Acta 1985; 44: 1201-1210
9 Hauptmann J, Kaiser B, Markwardt F. Anticoagulant action of synthetic tight binding inhibitors of thrombin in vitro and in vivo. Thromb Res 1985; 39: 771-775
10 Markwardt F, Hoffmann A, Stürzebecher J. Influence of thrombin inhibitors on the thrombin-induced activation of human blood platelets. Haemostasis 1983; 13: 227-233
11 Markwardt F, Nowak G, Hoffmann J. Comparative studies on thrombin inhibitors in experimental microthrombosis. Thromb Haemostas 1983; 49: 235-237
12 Wessler S. Thrombosis in the presence of vascular stasis. Am J Med 1962; 33: 648-666
13 Philp RB, Francey I, Warren BA. Comparison of antithrombotic activity of heparin, ASA, sulfinpyrazone and VK 744 in a rat model of arterial thrombosis. Haemostasis 1978; 7: 282-293
14 Smith JR, White AM. Fibrin, red cell and platelet interactions in an experimental model of thrombosis. Br J Pharmacol 1982; 77: 29-38
15 Glusa E, Hoffmann A, Markwardt F. Influence of benzamidine derivatives on thrombin-induced platelet reactions. Folia Haematol (Leipz) 1982; 109: 098-106