title: [Influence of new N,N'-substituted piperazines on thrombin-induced platelet activation].
abstract: 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.
authors.forename: O C
authors.initials: OC
authors.lastname: Veselkina
authors.forename: N N
authors.initials: NN
authors.lastname: Petrishchev
authors.forename: L V
authors.initials: LV
authors.lastname: Vasina
authors.forename: M E
authors.initials: ME
authors.lastname: Borovitov
authors.forename: A V
authors.initials: AV
authors.lastname: Seliutin
authors.forename: S V
authors.initials: SV
authors.lastname: Chepanov
authors.forename: S A
authors.initials: SA
authors.lastname: Sel'kov
mesh_terms: D000328:Adult; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D015398:Signal Transduction; D013917:Thrombin / Q000494:pharmacology*; D013931:Thromboxanes / Q000378:metabolism
chemical_list: D007295:Inositol Phosphates; D019007:P-Selectin; D010879:Piperazines; D010975:Platelet Aggregation Inhibitors; D013931:Thromboxanes; D013917:Thrombin; D001241:Aspirin; D002118:Calcium