The Influence of Molsidomine and Its Active Metabolite SIN-1 on Fibrinolysis and Platelet Aggregation

Abstract

Molsidomine and its active metabolite SIN-1 were examined in humans and animals for platelet suppressant and fibrinolytic activities. Following oral administration of molsidomine at doses of 6 or 15 mg/kg to rabbits, their blood platelets in PRP ex vivo required higher threshold concentrations of ADP, AA and thrombin to be aggregated. Unlike molsidomine, SIN-1 when infused (10 and 20 micrograms/kg i.v.) into anaesthetized cats caused a release of a substance disaggregating platelet clumps which had adhered to blood superfused collagen strip. The appearance of this unstable disaggregating substance was prevented by the pretreatment of cats with aspirin (50 mg/kg i.v.). It is suggested that SIN-1 may promote formation of a PGI2-like substance. In humans shortening of euglobulin clot lysis time was observed 60 min after a single ingestion of 2 mg of molsidomine. This fibrinolytic effect of molsidomine was not abolished by the pretreatment of patients with aspirin. Neither molsidomine nor SIN-1 activated fibrinolysis in preformed euglobulin clots in vitro.