SELECTIVE-INHIBITION OF NS-398 ON PROSTANOID PRODUCTION IN INFLAMED TISSUE IN RAT CARRAGEENAN-AIR-POUCH INFLAMMATION

NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methane sulphonamide), a new ly synthesized potent non-steroidal anti-inflammatory drug (NSAID) has a much lesser degree of toxicity, as compared with presently availabl e NSAIDs. We have investigated the inhibition of prostanoid production in inflammatory exudate, gastric mucosa and renal papillary tissue, f ollowing oral administration to carrageenan-air-pouch rats. The ID50 v alues 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 c ontrast, indomethacin decreased the PGE2 concentration in the inflamma tory 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, respec tively. The same tendency was seen for 6-keto-prostaglandin F1 and thr omboxane B2. Moreover, NS-398 inhibited excess PGE2 production in infl amed tissue but did not affect physiological production of PGE2 in non -inflamed tissue. Indomethacin, in both inflamed and non-inflamed tiss ues, inhibited PGE2 production to the same degree. These results indic ated that NS-398 has some specificity for inflamed tissue, by inhibiti ng prostanoid synthesis, and this effect may explain the decreased sid e-effects of this drug.