A study of the novel anti-inflammatory agent florifenine topical anti-inflammatory activity and influence on arachidonic acid metabolism and neutrophil functions

Naunyn Schmiedebergs Arch Pharmacol. 1995 Mar;351(3):298-304. doi: 10.1007/BF00233250.

Abstract

We have evaluated the effects of the novel anti-inflammatory agent florifenine, 2-(1-Pyrrolidinyl)ethyl N-[7-(trifluoromethyl)-4-quinolyl]anthranilate, on topical inflammation in mice, free radical-mediated reactions, arachidonic acid metabolism and some neutrophil functions. Topical administration of florifenine produced dose-related anti-inflammatory activity in 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and with a lower potency, in the response induced by arachidonic acid (AA). Florifenine also inhibited neutrophil migration and PGE2 content in the inflammed ears. In human whole blood, florifenine was a potent and selective inhibitor of TXB2 generation. This anti-inflammatory agent did not exert antioxidant effects but inhibited elastase release in human neutrophils without affecting superoxide anion generation. Florifenine administration to mice dose-dependently inhibited leukocyte migration and PGE2 levels in the air pouch inflammation induced by zymosan. These results demonstrate the topical anti-inflammatory activity of florifenine and provide a basis for understanding the mechanisms involved in the inhibitory effects of this agent on inflammatory responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Aminoquinolines / pharmacology*
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology
  • Arachidonic Acid / metabolism*
  • Arachidonic Acid / pharmacology
  • Cell Survival / drug effects
  • Edema / drug therapy
  • Eicosanoids / biosynthesis
  • Free Radical Scavengers
  • Humans
  • Hydroxyl Radical / metabolism
  • In Vitro Techniques
  • Leukocyte Elastase
  • Lipid Peroxidation / drug effects
  • Mice
  • Neutrophils / drug effects*
  • Neutrophils / enzymology
  • Neutrophils / metabolism
  • Pancreatic Elastase / metabolism
  • Pyrrolidines / pharmacology*
  • Rats
  • Superoxides / metabolism
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Aminoquinolines
  • Anti-Inflammatory Agents
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Eicosanoids
  • Free Radical Scavengers
  • Pyrrolidines
  • Superoxides
  • Arachidonic Acid
  • Hydroxyl Radical
  • Pancreatic Elastase
  • Leukocyte Elastase
  • Tetradecanoylphorbol Acetate
  • florifenine