[Effect of alpha-(p-thenoylphenyl)-propionic acid (TN-762) on acute inflammatory reactions and prostaglandin biosynthesis].
A series of compounds with the general structure of phenylpropionic acid was originally synthesized for anti-inflammatory screening. The title compound, TN-762, showed marked anti-inflammatory and analgesic activities and was less toxic. This compound was the same as suprofen which was reported by Janssen to have potent anti-inflammatory and anti-writhing activities. Effects of TN-762 on acute inflammatory reactions and prostaglandin biosynthesis were investigated in animal models and findings compared to those of ketoprofen and indomethacin. TN-762 showed a dose-dependent inhibition at low doses of 5-20 mg/kg, p.o. on an increased vascular permeability induced by histamine in rats and by acetic acid in mice and carrageenin-induced paw edema in rats. The anti-inflammatory activity of TN-762 was much the same as that of ketoprofen and indomethacin. The inhibitory effect of TN-762 on carrageenin-induced paw edema was not affected by successive administration for 14 days and/or by adrenalectomy. The compound was more active than the two reference compounds in inhibiting ultraviolet erythema in guinea pigs. TN-762 inhibited markedly the arachidonic acid potentiation of carrageenin-induced edema in rat paw, the sudden death following intraveneous administration of arachidonic acid to rabbits and the diarrhea produced by endotoxin in mice, all considered to be induced by biosynthetic prostaglandins. The activities of TN-762 were the same or were more potent than those of ketoprofen and indomethacin. On the contrary, the ulcerogenic activity of TN-762 on the gastrointestinal tract in rats was significantly less than that of ketoprofen and indomethacin. From the above results, TN-762 proved to be a potent inhibitor of acutely-induced inflammation and of prostaglandin biosynthesis, however, the ulcerogenic effects were comparatively diminished.
D000818:Animals; D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors; D002199:Capillary Permeability / Q000187:drug effects; D003967:Diarrhea / Q000188:drug therapy; D004353:Drug Evaluation, Preclinical; D004487:Edema / Q000188:drug therapy; D004890:Erythema / Q000188:drug therapy; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D010437:Peptic Ulcer / Q000139:chemically induced; D010666:Phenylpropionates / Q000009:adverse effects / Q000494:pharmacology*; D011453:Prostaglandins / Q000096:biosynthesis*; D011817:Rabbits; D051381:Rats; D013329:Structure-Activity Relationship; D013496:Suprofen / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D001095:Arachidonic Acids; D010666:Phenylpropionates; D011453:Prostaglandins; D013496:Suprofen