ANTIPLATELET ACTIONS OF 2-(4-[1-(2-CHLOROPHENYL)PIPERAZINYL]) THYL-2,3-DIHYDROIMIDAZO[1,2-C]QUINAZOLIN-5(6H)-ONE COMPOUND

The new quinazolinone derivative,2-{4-[1-(2-chlorophenyl)piper azinyl] } 3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(CK53), inhibited platele t aggregation and ATP release induced by arachidonic acid, collagen, P AF and U46619 in washed rabbit platelets. In human platelet-rich plasm a CK53 also significantly suppressed the platelet aggregation and ATP release challenged by epinephrine and ADP. The thromboxane B-2 formati on of rabbit washed platelets caused by collagen and thrombin was redu ced by CK53 but that induced by arachidonic acid. CK53 inhibited the i ntracellular calcium increase stimulated by collagen and thrombin in q uin-2/AM-loaded rabbit platelets. Phosphoinositides breakdown caused b y collagen, U46619, PAF and thrombin was inhibited by CK53. CK53 also suppressed the aggregation of elastase-treated human platelets induced by fibrinogen but no alteration in platelet cyclic-AMP level. In conc lusion, these data indicate that antiplatelet effect of CK53 may be ma inly due to the direct inhibition of phosphoinositides breakdown.