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.