The influence of molsidomine and its active metabolite SIN-1 on fibrinolysis and platelet aggregation.
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.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D002415:Cats; D011464:Epoprostenol / Q000096:biosynthesis; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008981:Molsidomine / Q000031:analogs & derivatives; D010069:Oxadiazoles / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D011817:Rabbits; D013558:Sydnones / Q000008:administration & dosage / Q000494:pharmacology*
D010069:Oxadiazoles; D013558:Sydnones; C002385:linsidomine; D000244:Adenosine Diphosphate; D008981:Molsidomine; D011464:Epoprostenol; D001241:Aspirin