Piretanide: A New Synthetic Fibrinolytic and Anti-Platelet Agent

Summary

Piretanide, 4-phenoxy-3-(l-pyrrolidinyl)-5-sulfamoyl benzoic acid, a potent diuretic, enhances endogenous plasma fibrinolytic activity after a single dose of 6 mg administered orally. Acceleration of fibrinolytic activity becomes manifest within 1 h, reaches its peak in 3 h and is associated with little change in fibrinogen, however, it is accompanied with diminished urokinase excretion initially. Piretanide does not cause lysis of fibrin in vitro in any concentration. Primary platelet aggregation, induced by adenosine-diphosphate, is inhibited by piretanide, in vivo. In in vitro experiments piretanide leads to effective inhibition of ADP-induced platelet aggregation with complete inhibition at 5 mM concentration. Piretanide, after ingestion of a single dose of 6 mg, causes highly significant decrease of platelet factor-4 release.

Keywords

Piretanide - Synthetic fibrinolytic agent - Anti-platelet agent Platelet factor-4 release - Diuretic

• References

• 1 Singh I, Chohan IS. Reversal of abnormal fibrinolytic activity, blood coagulation factors and platelet function in high altitude pulmonary oedema with frusemide. Int J Biometeor 1973; 17: 73-81
• 2 Singh I, Chohan IS. Adverse changes in fibrinolysis, blood coagulation and platelet function in high altitude pulmonary oedema and their role in its pathogenesis. Int J Biometeor 1974; 18: 33-45
• 3 Chohan IS. First few days at high altitude and furosemide. Int Rev Army Navy Air Force Med Serv, Liege (Belgique) 1980; 53: 745-753
• 4 Chohan IS. Blood coagulation changes at high altitude. Def Sci J 1984; 34: 361-379
• 5 Lawrence JR, Ansari AF, Elliott HL, Sumner DJ, Brunton GF, Whiting B, Whitesmith R. Kinetic and dynamic comparison of piretanide and furosemide. Clin Pharmacol Therap 1978; 23: 558-565
• 6 Astrup T, Mullertz S. The fibrin plate method for estimating fibrinolytic activity. Arch Biochem 1952; 40: 346-351
• 7 Chohan IS, Singh I, Vermylen J, Verstraete M. Effect of furosemide on plasma fibrinolytic activity and urokinase excretion. Exp Hematol 1977; 5: 153-157
• 8 Ratnoff OD, Menzie C. A new method for determination of fibrinogen in small samples of plasma. J Lab Clin Med 1951; 37: 316-320
• 9 Harada K, Zucker MB. Simultaneous development of platelet factor 4 activity and release of 14C-Serotoniny. Thrombos Diathes Haemorrh 1971; 25: 41-46
• 10 Chohan IS, Singh I, Vermylen J. Furosemide: Its role on certain platelet functions. Acta Clin Belgica 1977; 32: 39-43
• 11 Bom GV R. Strong inhibition by 2-chloroadenosine of the aggregation of blood platelets by adenosine diphosphate. Nature 1964; 202: 95-96
• 12 Malmsten C, Gramstrom E, Samuelsson B. Cyclic AMP inhibits synthesis of prostaglandin endoperoxides (PGG2) in human platelets. Biochem Biophys Res Commun 1976; 68: 569-576
• 13 Holger-Madsen T. Heparin resistance in acute coronary occlusion measured by the plasma heparin thrombin time. Acta Haematol (Basel) 1960; 23: 195-207
• 14 O’Brien JR, Etherington MD, Jamieson S, Lowford P, Sussex J, Lincolin SV. Heparin neutralizing activity in the diagnosis of acute myocardial infarction. J Clin Path 1975; 28: 975-979
• 15 Aimer LO, Nilsson IM. On fibrinolysis in diabetes mellitus. Acta Med Scand 1975; 198: 101-106
• 16 Walker ID, Davidson JF, Hutton I, Lawrie TD. Disordered "fibrinolytic potential" in coronary heart disease. Thromb Res 1977; 10: 509-520
• 17 Davidson JF, Walker ID. Synthetic fibrinolytic agents. Prog Cardiovasc Dis 1979; 21: 375-396