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InflammoPharmacology

, 12:521 | Cite as

NMI-1182, a gastro-protective cyclo-oxygenase-inhibiting nitric oxide donor

  • James L. Ellis
  • Michael E. Augustyniak
  • Edward D. Cochran
  • Richard A. Earl
  • David S. Garvey
  • Laura J. Gordon
  • David R. Janero
  • Subhash P. Khanapure
  • L. Gordon Letts
  • Terry L. Melim
  • Madhavi G. Murty
  • David J. Schwalb
  • Matthew J. Shumway
  • William M. Selig
  • A. Mark Trocha
  • Delano V. Young
  • Irina S. Zemtseva
Article

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammation and to provide pain relief but suffer from a major liability concerning their propensity to cause gastric damage. As nitric oxide (NO) is known to be gastro-protective we have synthesized a NO-donating prodrug of naproxen named NMI-1182. We evaluated two cyclo-oxygenase (COX)-inhibiting nitric oxide donors (CINODs), NMI-1182 and AZD3582, for their ability to be gastroprotective compared to naproxen and for their anti-inflammatory activity. NMI-1182 and AZD3582 were found to produce similar inhibition of COX activity to that produced by naproxen. Both NMI-1182 and AZD3582 produced significantly less gastric lesions after oral administration than naproxen. All three compounds effectively inhibited paw swelling in the rat carrageenan paw edema model. In the carrageenan air pouch model all three compounds significantly reduced PGE2 levels in the pouch exudate but only NMI-1182 and naproxen inhibited leukocyte influx. These data demonstrate that NMI-1182 has comparable anti-inflammatory activity to naproxen but with a much reduced likelihood to cause gastric damage.

Key words

Non-steroidal anti-inflammatory drug (NSAID) nitric oxide gastro-protection gastric damage naproxen CINOD anti-inflammatory cyclo-oxygenase 

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Copyright information

© VSP 2005

Authors and Affiliations

  • James L. Ellis
    • 1
  • Michael E. Augustyniak
    • 1
  • Edward D. Cochran
    • 1
  • Richard A. Earl
    • 1
  • David S. Garvey
    • 1
  • Laura J. Gordon
    • 1
  • David R. Janero
    • 1
  • Subhash P. Khanapure
    • 1
  • L. Gordon Letts
    • 1
  • Terry L. Melim
    • 1
  • Madhavi G. Murty
    • 1
  • David J. Schwalb
    • 1
  • Matthew J. Shumway
    • 1
  • William M. Selig
    • 1
  • A. Mark Trocha
    • 1
  • Delano V. Young
    • 1
  • Irina S. Zemtseva
    • 1
  1. 1.NitroMed Inc.LexingtonUSA

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