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.
Singh
Vijay Pal
VP
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh - 160 014, India.
Patil
Chandrashekhar S
CS
Kulkarni
Shrinivas K
SK
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D005620:Freund's Adjuvant; D006099:Granuloma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D051379:Mice; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014110:Touch
D000085:Acetates; D000893:Anti-Inflammatory Agents; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D011758:Pyrroles; D002351:Carrageenan; D005620:Freund's Adjuvant; C088092:licofelone; D007213:Indomethacin