Y-590 (A new pyridazinone derivative), a potent anti-thrombotic agent — I. Effect on platelet function

Abstract

The effect of 6-(2,3,4,5-tetrahydro-5-methyl-3-oxopyridazine-6-yl)-1,2,3,4-tetrahydro-l-methyl quinolin -2-one (Y-590) on platelet function was investigated. Y-590 inhibited platelet aggregation induced by a variety of aggregating agents in platelet rich plasma obtained from various species. In rat platelet, its IC 50 for ADP-induced aggregation was 9 ng/ml. Y-590 also showed a disaggregative effect on aggregated platelets. The inhibitory effect of Y-590 on ADP-induced aggregation of rabbit platelet was synergistically potentiated by prostaglandin I 2. Potent anti-aggregatory activity was also found in ex vivo experiments using rats and rabbits given oral doses of 0.1 and 0.01 mg/kg respectively. In vitro, Y-590 inhibited platelet release reaction induced by collagen. Single oral doses of Y-590 reduced guinea pig platelet retention. Y-590 had no effect on MDA formation in vitro and PGI2 generation in rat vessel walls ex vivo. These results show that Y-590 is a potent anti-aggregating agent that may be useful in preventing thrombotic disorders.