Antiplatelet actions of 2-{4-[1-(2-chlorophenyl)piperazinyl]} methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one compound

Abstract

The new quinazolinone derivative,2-{4-[1-(2-chlorophenyl)piperazinyl]} methyl-2,3-dihydroimidazo[1,2-c]quinazolin-5(6H)-one(CK53), inhibited platelet aggregation and ATP release induced by arachidonic acid, collagen, PAF and U46619 in washed rabbit platelets. In human platelet-rich plasma CK53 also significantly suppressed the platelet aggregation and ATP release challenged by epinephrine and ADP. The thromboxane B 2 formation of rabbit washed platelets caused by collagen and thrombin was reduced by CK53 but that induced by arachidonic acid. CK53 inhibited the intracellular calcium increase stimulated by collagen and thrombin in quin-2/AM-loaded rabbit platelets. Phosphoinositides breakdown caused by 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 conclusion, these data indicate that antiplatelet effect of CK53 may be mainly due to the direct inhibition of phosphoinositides breakdown.