Anti‐inflammatory effect of licofelone against various inflammatory challenges

We investigated the pharmacological profile of licofelone [6‐(4‐chlorophenyl)‐2,3‐dihydro‐2,2‐dimethyl‐7‐phenyl‐1H‐pyrrolizine‐5‐acetic acid] against different inflammogens. The anti‐inflammatory and anti‐hyperalgesic effect of licofelone (2, 30 and 100 mg/kg, p.o.) against all the challenges was statistically significant ( P < 0.05) when compared with control and indomethacin (10 mg/kg, p.o.). The ED 50 value of 19.1 mg/kg (onset by 2 h, duration: short), 13.0 mg/kg and 16.8 mg/kg (onset by 1 h, duration: long) was observed for licofelone against carrageenan‐, arachidonic acid‐ and bradykinin‐induced paw oedema, respectively. Similarly, licofelone showed ED 50 value of 47.6 mg/kg (onset by 1 h, duration: long), 92.2 mg/kg (onset by 1 h, duration: medium), and 78.6 mg/kg (onset by 2 h, duration: medium) against carrageenan‐, arachidonic acid‐ and bradykinin‐induced mechanical hyperalgesia, respectively. The rank order of potency based on percent inhibition and percent reversal against inflammation and mechanical hyperalgesia, respectively, was found to be licofelone > indomethacin. Moreover, licofelone (10–100 mg/kg, p.o.) significantly ( P < 0.05) and dose‐dependently prevented the Freund's adjuvant‐induced increased vascularity in mice (vascularity index; 10 mg/kg: 0.059 ± 0.015; 20 mg/kg: 0.048 ± 0.004; 30 mg/kg: 0.039 ± 0.012; 100 mg/kg: 0.025 ± 0.015 vs. control: 0.0285 ± 0.003). Furthermore, the results suggested that dual inhibitors of cyclooxygenase and lipoxygenase like licofelone provide an effective control of inflammation and hyperalgesia against acute inflammation/hyperalgesia in rats and mice.