EFFECT OF VINTOPEROL ON PLATELET-AGGREGATION AND EXPERIMENTAL THROMBOSIS

The platelet aggregation inhibitory and antithrombic effect of the new peripheral circulation enhancing compound vintoperol (RGH-2981, CAS 1 06498-99-1) was studied. In vitro, vintoperol inhibited the aggregatio n response to collagen in platelet-rich plasma mice, rats, rabbit and dogs. It was found to be highly effective in preventing midce from acu te pulmonary thromboemolic death induced by adenosine diphosphate (ADP ) or collagen. After oral dose of 10 mg/kg the percentage of survivors increased from 9 to 60% and from 13 to 73%, respectively. In the ''mo use antithrombic assay'' it was protective only at the 3 mg/kg dose. S udden death of mice by hardened red blood cell suspension was not prot ected by vintoperol. In mice receiving 30 mg/kg vintoperol orally, the inhibition of aggregation respone to collagen, ADP and ADP/epinephrin e by 15, 33 and 37%, respectively, was associated with a substantial i ncrease in bleeding time. In a rat multifactorial thrombosis model the 10 mg/kg p.o. dose was also sufficient to obtain significant antithro mbotic effect (p < 0.01). Results of these experiments indicate that v intoperol with platelet aggregation both in vitro and in vivo and poss esses potent antithrombotic effect in thrombosis models in which plate let activation is mainly involved.