NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects

Aliment Pharmacol Ther. 1997 Feb;11(1):69-79. doi: 10.1046/j.1365-2036.1997.115286000.x.


Background: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID.

Methods: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis.

Results: NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNF alpha to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen.

Conclusion: NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesics / pharmacokinetics
  • Analgesics / toxicity*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacokinetics
  • Anti-Inflammatory Agents, Non-Steroidal / toxicity*
  • Ileal Diseases / blood
  • Ileal Diseases / chemically induced
  • Male
  • Metabolic Clearance Rate
  • Naproxen / analogs & derivatives
  • Naproxen / pharmacokinetics
  • Naproxen / toxicity*
  • Peptic Ulcer / blood
  • Peptic Ulcer / chemically induced*
  • Rats
  • Rats, Wistar
  • Tumor Necrosis Factor-alpha / analysis


  • Analgesics
  • Anti-Inflammatory Agents, Non-Steroidal
  • Tumor Necrosis Factor-alpha
  • Naproxen