Effect of NS-398, a new nonsteroidal anti-inflammatory agent, on gastric ulceration and acid secretion in rats.
The ulcerogenic activity of NS-398 was compared with that of indomethacin and the effects of NS-398 on stress-induced ulceration, gastric acid secretion and gastric mucosal prostaglandin (PG) contents were investigated in rats. NS-398 in a single dose of up to 1,000 mg/kg, p.o. did not significantly cause gastric ulceration while other nonsteroidal anti-inflammatory drugs such as, loxoprofen, indomethacin, diclofenac and ibuprofen, produced distinct gastric lesions. In cases of stress-induced ulcerations, NS-398 at 30 mg/kg, p.o. had no significant influence while indomethacin markedly potentiated the ulceration in a dose dependent manner. In basal gastric secretion studies, both NS-398 and indomethacin decreased secretion volume and acidity. However, in the 2-deoxy-D-glucose-stimulated gastric acid secretion study, NS-398 had no significant influence on gastric secretions while indomethacin significantly potentiated the secretion. Both NS-398 and indomethacin to much the same extent significantly decreased prostaglandin E2 (PGE2) contents in inflammatory tissue. However, with respect to gastric mucosal PGE2 contents, NS-398 did not decrease PGE2 contents while indomethacin significantly decreased the contents. It would thus appear that the absence of ulcerogenic properties of NS-398 is due to a relative lack of activity in inhibiting gastric PG synthesis.
Arai
I
I
Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Hamasaka
Y
Y
Futaki
N
N
Takahashi
S
S
Yoshikawa
K
K
Higuchi
S
S
Otomo
S
S
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D007213:Indomethacin / Q000009:adverse effects; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology*; D010437:Peptic Ulcer / Q000209:etiology; D051381:Rats; D017208:Rats, Wistar; D013312:Stress, Physiological; D013449:Sulfonamides / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009578:Nitrobenzenes; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D007213:Indomethacin