title: Tissue-selective inhibition of prostaglandin synthesis in rat by tepoxalin: anti-inflammatory without gastropathy?
abstract: BACKGROUND
  Inhibition of prostaglandin synthesis is likely a primary mechanism for both the anti-inflammatory and ulcerogenic effects of nonsteroidal anti-inflammatory drugs (NSAIDs). The present study examined the mechanism underlying the ability of a novel anti-inflammatory drug, tepoxalin, to suppress prostaglandin synthesis without inducing gastric mucosal injury.
  
  
  METHODS
  The effects on prostaglandin synthesis by various tissues of tepoxalin, diclofenac, and indomethacin were examined in vivo and in vitro. These compounds were also studied in two inflammation models. The capacity of indomethacin and tepoxalin to induced antral ulceration in the rabbit was compared.
  
  
  RESULTS
  In most tissues, tepoxalin was a weaker inhibitor of prostaglandin synthesis than the two NSAIDs. However, at a site of peripheral inflammation, tepoxalin was comparable with the NSAIDs in suppressing prostaglandin synthesis and in exerting anti-inflammatory effects. Indomethacin induced penetrating antral ulcers in rabbits whereas tepoxalin produced no detectable mucosal injury.
  
  
  CONCLUSIONS
  The ability of tepoxalin to suppress inflammation without causing gastric mucosal injury appears to be related to its differential suppression of prostaglandin synthesis in various tissues. Compounds that selectively inhibit prostaglandin synthesis at sites of inflammation may represent a class of anti-inflammatory drugs without detrimental effects on the stomach.
authors.affiliation: Gastrointestinal Research Group, University of Calgary, Alberta, Canada.
authors.forename: J L
authors.initials: JL
authors.lastname: Wallace
authors.forename: D M
authors.initials: DM
authors.lastname: McCafferty
authors.forename: L
authors.initials: L
authors.lastname: Carter
authors.forename: W
authors.initials: W
authors.lastname: McKnight
authors.forename: D
authors.initials: D
authors.lastname: Argentieri
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D005753:Gastric Mucosa / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008297:Male; D009928:Organ Specificity; D011453:Prostaglandins / Q000096:biosynthesis*; D011720:Pyrazoles / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D011720:Pyrazoles; C073135:tepoxalin