Effect of ETH615, an inhibitor of leukotriene synthesis and IL-8 gene expression, on murine dermatoses

Agents Actions. 1993:39 Spec No:C166-8. doi: 10.1007/BF01972755.

Abstract

ETH615 (4-[2-quinolylmethoxy]-N-[3-fluorobenzyl]-phenylaminometh yl-4-benzoic acid) is a potent inhibitor of leukotriene biosynthesis in A23187-stimulated leukocytes, and of IL-8 gene expression in LPS-stimulated PBMC. It shows anti-inflammatory activity in a canine model of dermal inflammation. A topical formulation is present in phase II clinical trials. In the present study the effect of ETH615 on oxazolone-induced acute inflammation and phorbol ester-induced chronic inflammation in the mouse ear was investigated. Betamethasone (0.04 mg/ear) and ETH615 (1-1.5 mg/ear) significantly inhibited both the oedema formation and the PMN infiltration. The cream and ointment formulations of ETH615 developed for clinical studies were equally active. ETH615 is thus an anti-inflammatory agent in these murine models of dermatosis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Betamethasone / therapeutic use
  • Dermatitis / drug therapy*
  • Disease Models, Animal
  • Ear
  • Edema / chemically induced
  • Edema / drug therapy
  • Gene Expression / drug effects
  • Interleukin-8 / genetics
  • Leukotriene B4 / antagonists & inhibitors*
  • Mice
  • Oxazolone
  • Peroxidase / metabolism
  • Quinolines / administration & dosage
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • T-Lymphocytes / drug effects
  • Tetradecanoylphorbol Acetate

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-8
  • Quinolines
  • ETH 615
  • Oxazolone
  • Leukotriene B4
  • Betamethasone
  • Peroxidase
  • Tetradecanoylphorbol Acetate