[Influence of new N,N'-substituted piperazines on thrombin-induced platelet activation].

We have studied the influence of new N,N'-substituted piperazines with variable nature of the linker between piperazine and aromatic cycles (carbonyl group in VR-0411 versus sulfonyl group in VR-0511) on thrombin-induced platelet aggregation, cytoplasmic Ca2+ mobilization in platelets, and P-selectin exposure on the platelet plasma membrane. The inhibitory effect of VR-0511 on platelet aggregation exceeds the effects of the reference compound aspirin and VR-0411 by 35 and 42%, respectively (p < or = 0.01). The effects of test compounds on the mobilization of cytoplasmic Ca2+ in platelets and P-selectin exposure indicate that VR-0411 and VR-0511 inhibit platelet activation in these tests by 28 and 61%, (p < or = 0.01) and 34 and 58% (p < or = 0.01), respectively. The possible targets for VR-0411 and VR-0511 are thromboxane and inositol triphosphate-dependent (IP3 formation) pathways of activation signal transfer.