Description
Cross-
talk between lipoxygenase (LO) and cyclooxygenase (COX) pathways has been observed in human osteoarthritic synovial explants which creates an arachidonic acid shunting phenomenon, stimulating interleukin-
1β (IL-
1β) synthesis. Licofelone is a dual inhibitor of cyclooxygenase (COX) and lipoxygenase (LO) pathways, that decreases levels of prostaglandin E
2, leukotriene B
4, and lipoxins and prevents lipopolysaccharide-
stimulated IL-
1β expression. The IC
50 values for inhibition of human thrombocyte COX and human 5-
LO are 0.16 μM and 0.23 μM, respectively. Unlike other non-
steroidal anti-
inflammatory drugs, licofelone causes little or no damage to the gastric mucosa in rabbit parietal cells. This is presumably the result of licofelone’s affects on acid-
secretory mechanisms, mediated by the inhibition of 5-
LO activity.
in vitro
the 5-lox and cox inhibitory effect of licofelone was firstly identified via bovine thromobocyte intact cell assay and intact bovine pmn leukocytes. licofelone was also reported to inhibit pge2 in a dose-dependent manner in human whole blood assay. moreover, licofelone was found to suppress in vitro generation of reactive oxygen species and to reduce release of elastase from pmn leukocytes. all above findings revealed that licofelone had an inhibitory effect on cox-1/-2 and 5-lox. [1]
in vivo
the pharmacodynamic properties of licofelone were evaluated in various animal models and compared with those of commonly used nsaids. based on studies from a rat model of incisional pain, orally administration of licofelone had a longer duration of action and was more effective than indomethacin and zileuton. [1]
IC 50
inhibitor of cox-1, cox-2 and 5-lox with ic50 values of 0.16 m, 0.37 m and 0.23 m respectively in human.
