Since a newly synthesized nonsteroidal antiinflammatory
drug (
NSAID) having weaker effects on gastrointestinal tract, 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)
propionic acid (CN-100), was found to markedly inhibit rat paw
edema induced by
carrageenin and other phlogists, the effects of the
drug on other acute inflammatory reactions and
prostaglandins (PGs)-related reactions were compared with those of known
NSAID in this study. At even a large dose of
CN-100, 20 mg/kg, the
drug did not significantly inhibit the increased vascular permeability induced by
histamine in rat skin, but
CN-100 could dose-dependently inhibit the increased vascular permeability induced by
acetic acid in mouse peritoneum. The inhibitory activity of
CN-100 in the latter was equivalent to that of
pranoprofen and
indometacin.
CN-100 exerted a potent inhibitory action on
erythema induced by UV irradiation, which was equal to and 3 times stronger than
pranoprofen and
indometacin in activity, respectively. Since PGs participate in these acute inflammatory reactions, the effects of
CN-100 on reactions relevant to PGs were examined. The
drug at dose levels lower than antiinflammatory doses could prevent acute death and
diarrhea induced by i.v. injection of
arachidonic acid in rabbits and
endotoxin in mice, respectively, suggesting that the
drug had a potent inhibitory action on biosynthesis of PGs. The adverse effects of
CN-100 on gastric and small intestinal mucosa was very weak, the activity being about one-tenth of that of
pranoprofen and
indometacin.