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  • Title: Pharmacological investigations of the new antiinflammatory agent 2-(10,11-dihydro-10-oxodibenzo[b,f]thiepin-2-yl)propionic acid. 2nd communication: inhibitory effects on acute inflammation and prostaglandin-related reactions.
    Author: Tsurumi K, Kyuki K, Niwa M, Mibu H, Fujimura H.
    Journal: Arzneimittelforschung; 1986 Dec; 36(12):1801-5. PubMed ID: 3105545.
    Abstract:
    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.
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