Effects of methylflavonolamine on platelet aggregation in rabbits

Effects of methylflavonolamine (SIPI- 549, 4 '-methyl-7-(2-hydroxy-3-isopropylaminopropoxy)-flavone hydrochloride) on platelet aggregation in rabbits were studied by optical method. The IC50 values for SIPI-049 to inhibit platelet aggregation induced by ADP, thrombin and collagen were 0.15, 0.29 and 0.04 mmol/L, respectively. SIPI-549, which depressed the maximal response of platelets to ADP,acted as a non-competitive antagonist of ADP. Dynamic study on intact platelets showed that the dissociation constants of ADP and SIPI-549 were 3.1 and 218 vmol/L, respectively. SIPI-549 inhibited the change in shape of platelets and shortened the lag phase in the wave of platelet aggregation induced by collagen. Propranolol had no obvious effect on platelet aggregation induced by ADP and thrombin, but inhibited collagen-induced platelet aggregation. SIPI-549 (30 mg/kg)/d x 5 im into rabbits also inhibited ADP-induced platelet aggregation. It is concluded that SIPI-549 is a potent inhibitor of rabbit platelet aggregation in vitro and in situ.