NS-398, a new anti-inflammatory agent, selectively inhibits prostaglandin G/H synthase/cyclooxygenase (COX-2) activity in vitro

Prostaglandins. 1994 Jan;47(1):55-9. doi: 10.1016/0090-6980(94)90074-4.


NS-398 is a novel anti-inflammatory and analgesic agent which produces much fewer gastrointestinal lesions in rats. Recently, two forms of cyclooxygenase have been identified: a COX-1 first purified from ram seminal vesicles and a newly discovered mitogen-inducible form (COX-2). Effects of NS-398 on activities of these two distinct forms of COX were investigated. COX-1 purified from ram seminal vesicles and COX-2 isolated from sheep placenta (purity was 70%) were used. The COX-1 activity was completely unaffected by 10(-4) M NS-398, whereas the COX-2 activity was concentration-dependently inhibited, the IC50 value being 3.8 x 10(-6) M. Indomethacin inhibited both COX-1 and COX-2 activity to the same degree, the IC50 values being 7.4 x 10(-7) M and 9.7 x 10(-7) M, respectively. The anti-inflammatory and analgesic effects of NS-398 were almost as potent as indomethacin, the effective dose range being 0.3 approximately 5 mg/kg in rats. The gastrointestinal lesions related to NS-398 were not significant following a dose of 1000 mg/kg given orally. NS-398 is the first documented agent to have selective inhibition for COX-2, which may result in the less gastrointestinal toxicity.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Female
  • Male
  • Nitrobenzenes / pharmacology*
  • Prostaglandin-Endoperoxide Synthases / drug effects*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Seminal Vesicles / enzymology
  • Sheep
  • Sulfonamides / pharmacology*


  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase Inhibitors
  • Nitrobenzenes
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Prostaglandin-Endoperoxide Synthases