Selective inhibition of NS-398 on prostanoid production in inflamed tissue in rat carrageenan-air-pouch inflammation

J Pharm Pharmacol. 1993 Aug;45(8):753-5. doi: 10.1111/j.2042-7158.1993.tb07103.x.

Abstract

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methane sulphonamide), a newly synthesized potent non-steroidal anti-inflammatory drug (NSAID) has a much lesser degree of toxicity, as compared with presently available NSAIDs. We have investigated the inhibition of prostanoid production in inflammatory exudate, gastric mucosa and renal papillary tissue, following oral administration to carrageenan-air-pouch rats. The ID50 values of NS-398 in the inflammatory exudate, gastric mucosa and renal papillary tissue were 0.18, 62.2 and 261.7 mg kg-1, respectively. In contrast, indomethacin decreased the PGE2 concentration in the inflammatory exudate, gastric mucosa and renal papillary tissue, with the same dose range, the ID50 values being 0.23, 0.14 and 0.15 mg kg-1, respectively. The same tendency was seen for 6-keto-prostaglandin F1 and thromboxane B2. Moreover, NS-398 inhibited excess PGE2 production in inflamed tissue but did not affect physiological production of PGE2 in non-inflamed tissue. Indomethacin, in both inflamed and non-inflamed tissues, inhibited PGE2 production to the same degree. These results indicated that NS-398 has some specificity for inflamed tissue, by inhibiting prostanoid synthesis, and this effect may explain the decreased side-effects of this drug.

Publication types

  • Comparative Study

MeSH terms

  • 6-Ketoprostaglandin F1 alpha / biosynthesis
  • Air Sacs / drug effects*
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Carrageenan
  • Dinoprostone / biosynthesis
  • Exudates and Transudates / metabolism
  • Gastric Mucosa / drug effects
  • Gastric Mucosa / metabolism
  • Indomethacin / pharmacology
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Kidney / drug effects
  • Kidney / metabolism
  • Nitrobenzenes / pharmacology*
  • Prostaglandins / biosynthesis*
  • Rats
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / drug therapy
  • Respiratory Tract Diseases / metabolism
  • Sulfonamides / pharmacology*
  • Thromboxane B2 / biosynthesis

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Nitrobenzenes
  • Prostaglandins
  • Sulfonamides
  • N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
  • Thromboxane B2
  • 6-Ketoprostaglandin F1 alpha
  • Carrageenan
  • Dinoprostone
  • Indomethacin