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

Summary

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 μg/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.

Keywords

Molsidomine - SIN-1 - Platelet aggregation - Fibrinolysis - Aspirin

• References

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