Analgesic and antiinflammatory effects of 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid in rat and mouse.
Analgesic and antiinflammatory effects of 2-(10,11-dihydro-10-oxo-dibenzo[b,f]thiepin-2-yl)propionic acid (CN-100) have been investigated pharmacologically in rats and mice. With bradykinin-induced pain responses, CN-100 proved to be the most potent of the commercial non-steroidal antiinflammatory drugs which were tested in rats: The potency of CN-100 was 4 times stronger than that of indometacin. The analgesic effect of CN-100 on writhing induced by acetic acid, adjuvant-induced hyperalgesia, and carrageenin-induced hyperalgesia, and the effect on AgNO3-induced arthralgia were equipotent to or a little weaker than those of indometacin, but stronger than that of diclofenac sodium. In mice, CN-100 was found to be as active as indometacin against peritonitis induced by acetic acid and pain responses induced by mechanical stimulus (pressure). Against the peritonitis induced by acetylcholine and phenyl-quinone, CN-100 showed inhibitory actions and its potencies were much stronger than those of aminophenazone (amino-pyrine) in mice. However, all the drugs tested failed to increase pain thresholds induced by thermal stimulus in rats and mice. CN-100 exerted potent inhibitory effects on carrageenin-induced acute inflammatory edema and adjuvant-induced arthritis. The antiinflammatory effect of CN-100 on the former was equal to that of indometacin, but weaker on the latter. The ulcerogenic activity of CN-100 was less potent than that of indometacin. These results indicate that CN-100 may produce its analgesic effects through a peripheral mechanism and be preferable for clinical use, especially for the treatment of inflammatory conditions accompanied by pain.
D000109:Acetylcholine / Q000037:antagonists & inhibitors; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001582:Benzothiepins / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005260:Female; D008297:Male; D051379:Mice; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001582:Benzothiepins; D009270:Naloxone; C051758:CN 100; D000109:Acetylcholine