We report the results from an interspecies comparison of the antiplatelet, antithrombotic, and hemorrhagic actions of
SR 121566A, a novel nonpeptide
antiplatelet agent with high affinity and specificity for the
GP IIb/IIIa complex.
SR 121566A exhibited in vitro antiplatelet activity against
adenosine diphosphate (
ADP)-induced aggregation with a rank order of potency [humans = baboons = dogs] > marmosets > guinea pigs > rabbits. These in vitro findings were predictive for the ex vivo antiplatelet potency after i.v. administration of
SR 121566A to dogs, guinea pigs, and rabbits [median effective dose (ED50) values, 0.02, 0.05, and 0.15 mg/kg]. The antiplatelet actions of
SR 121566A translated into an acute antithrombotic effect in an arteriovenous shunt model after i.v. administration in dogs, guinea pigs, rabbits, and marmosets (ED50, 0.08, 0.10, 0.50, and 0.007 mg/kg). Hemorrhagic effects of
SR 121566A were observed in guinea pigs and rabbits at doses that represented 2-3 times the antithrombotic ED50, whereas in marmosets, no
bleeding was observed at the antithrombotic ED90. These results demonstrate that
SR 121566A exhibits favorable actions in terms of antithrombotic potency and
hemostatic safety in different animal species, suggesting that, in humans,
SR 121566A will be a good candidate as an antithrombotic compound.