5-Lipoxygenase/cyclooxygenase inhibitors, possessing anti-inflammatory action and gastric safety due to cyclooxygenase-2 and 5-lipoxygenase inhibition and antiplatelet activity due to cyclooxygenase-1 blockade, would be beneficial in the treatment of ischemic disease because they may reduce, at the same time, inflammation, underlying the atherosclerotic process, and platelet activation, responsible for acute thrombotic events. In this study, we characterized the antiplatelet effects of the new 5-lipoxygenase/cyclooxygenase inhibitor licofelone ([2,2-dimethyl-6-(4-chlorophenyl)-7-phenyl-2,3,dihydro-1H- pyrrolizine-5-yl]-acetic acid. Licofelone completely prevented platelet aggregation induced in platelet-rich plasma by threshold aggregating concentrations of arachidonic acid (0.87±0.14 mM) at threshold inhibitory concentrations of 0.75±0.35 μM (n=5). Platelet-rich plasma aggregation induced by threshold aggregating concentrations of collagen/adrenalin (0.3±0.05 μg/ml and 0.4±0.1 μM, respectively) was reduced to 3.2±2% of control at licofelone 100 μM, (P2 (TxB2) production by all the agonists tested at concentrations between 0.5 and 50 μM. At this concentration, TxB2 production was reduced at values similar to those of unstimulated platelets. These results indicate that, at clinically relevant concentrations, licofelone exerts a potent antiplatelet effect mediated by the inhibition of cyclooxygenase-1 activity.
- Cyclooxygenase-lipoxygenase inhibitor
- Platelet aggregation, human
- Thromboxane A2
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience