Effect of vintoperol on platelet aggregation and experimental thrombosis

The platelet aggregation inhibitory and antithrombotic effect of the new peripheral circulation enhancing compound vintoperol (RGH-2981, CAS 106498-99-1) was studied. In vitro, vintoperol inhibited the aggregation response to collagen in platelet-rich plasma from mice, rats, rabbits and dogs. It was found to be highly effective in preventing mice from acute pulmonary thromboembolic death induced by adenosine diphosphate (ADP) or collagen. After the oral dose of 10 mg/kg the percentage of survivors increased from 9 to 60% and from 13 to 73%, respectively. In the "mouse antithrombotic assay" it was protective only at the 3 mg/kg dose. Sudden death of mice evoked by hardened red blood cell suspension was not protected by vintoperol. In mice receiving 30 mg/kg vintoperol orally, the inhibition of aggregation response to collagen, ADP and ADP/epinephrine by 15, 33 and 37%, respectively, was associated with a substantial increase in bleeding time. In a rat multifactorial thrombosis model the 10 mg/kg p.o. dose was also sufficient to obtain significant antithrombotic effect (p < 0.01). Results of these experiments indicate that vintoperol interferes with platelet aggregation both in vitro and in vivo and possesses potent antithrombotic effects in thrombosis models in which platelet activation is mainly involved.