Anti-inflammatory effect of licofelone against various inflammatory challenges

Fundam Clin Pharmacol. 2006 Feb;20(1):65-71. doi: 10.1111/j.1472-8206.2005.00387.x.

Abstract

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.

Publication types

  • Comparative Study

MeSH terms

  • Acetates / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Carrageenan
  • Cyclooxygenase Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Edema / chemically induced
  • Edema / prevention & control*
  • Female
  • Freund's Adjuvant
  • Granuloma / chemically induced
  • Granuloma / pathology
  • Granuloma / prevention & control*
  • Hyperalgesia / chemically induced
  • Hyperalgesia / prevention & control*
  • Indomethacin / pharmacology
  • Lipoxygenase Inhibitors / pharmacology
  • Mice
  • Pain Measurement
  • Pain Threshold / drug effects
  • Pyrroles / pharmacology*
  • Rats
  • Rats, Wistar
  • Time Factors
  • Touch

Substances

  • Acetates
  • Anti-Inflammatory Agents
  • Cyclooxygenase Inhibitors
  • Lipoxygenase Inhibitors
  • Pyrroles
  • Carrageenan
  • Freund's Adjuvant
  • licofelone
  • Indomethacin