NPC 15669, an antiinflammatory leucine derivative, reduces in vitro platelet aggregability in both swine and human plasma

Background: Leumedins inhibit cell adhesion to endothelium via blockage of integrin binding. We tested a hypothesis that the novel leucine derivate NPC 15669 will affect in vitro platelet aggregability (PA) in both human and swine plasma. Methods and Results: Platelet-rich plasma (PRP) was incubated with 200 μ-g and 400 μg of NPC 15669. Then PA was induced by ADP, collagen, thrombin, and ristocetin in the PRP without NPC 15669 and in NPC 15669 treated samples. We have found that PRP incubation with 200 μg of NPC 15669 significantly decreases PA compared to baseline in all three experimental groups in response to all agonists tested. When PRP was treated with 400 μg of NPC 15669, dose-dependent reduction of PA was observed only in the human control and swine groups, but not in patients with coronary atherosclerosis. Conclusions: Leumedins, known for their antiinflammatory properties, may have clinical applications related to their effect on platelet function. The mechanism of these effects is unknown, but may be related to the inhibition of platelet-endothelial binding.