NS-398, a novel non-steroidal anti-inflammatory drug with potent analgesic and antipyretic effects, which causes minimal stomach lesions.
1. NS-398 (N-[2-cyclohexyloxy-4-nitrophenyl] methanesulfonamide) is a new non-steroidal anti-inflammatory drug (NSAID) with analgesic and antipyretic effects. 2. The anti-inflammatory potency of NS-398 in rat carrageenin-induced edema was as potent as that of indomethacin and 8 times more potent than diclofenac. In rat adjuvant arthritis, NS-398 showed a therapeutic effect comparable to that seen with loxoprofen but less than that seen with indomethacin and diclofenac. 3. The analgesic potency of NS-398 in rat adjuvant arthritic pain was much the same as that of indomethacin, and was about 3-5 times higher than that of diclofenac and loxoprofen. In the Randall-Selitto method in rats, NS-398 was 2-7 times as potent as loxoprofen, diclofenac and indomethacin. In acetic acid-induced writhing in mice, NS-398 was equipotent to indomethacin and diclofenac. 4. In LPS-induced fever in rats, NS-398 was 1.5-4.5 times as potent as loxoprofen and indomethacin, but less potent than diclofenac. 5. NS-398 produced little gastric ulceration in doses of up to 1000 mg/kg, while reference drugs produced distinct stomach lesions in doses of 10-30 mg/kg. 6. NS-398 inhibited prostaglandin (PG) endoperoxide synthase from sheep seminal vesicle microsomes less potent than that of ibuprofen.
Futaki
N
N
Research Center, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
Yoshikawa
K
K
Hamasaka
Y
Y
Arai
I
I
Higuchi
S
S
Iizuka
H
H
Otomo
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000633:toxicity; D001169:Arthritis, Experimental / Q000188:drug therapy; D002351:Carrageenan; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004008:Diclofenac / Q000494:pharmacology / Q000633:toxicity; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D007052:Ibuprofen / Q000494:pharmacology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology* / Q000633:toxicity; D010146:Pain / Q000188:drug therapy; D010666:Phenylpropionates / Q000494:pharmacology / Q000633:toxicity; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013276:Stomach Ulcer / Q000139:chemically induced* / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology* / Q000633:toxicity
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D009578:Nitrobenzenes; D010666:Phenylpropionates; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004008:Diclofenac; C040656:loxoprofen; D002351:Carrageenan; D011451:Prostaglandin-Endoperoxide Synthases; D007052:Ibuprofen; D007213:Indomethacin