Pharmacological profiles of 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate and 2-[(2-carboxyphenoxy)-carbonyl]phenyl-1-(4-chlorobenzoyl)-5-meth oxy-2- methylindole-3-acetate, new antiinflammatory agents.
When the effects of new antiinflammatory drugs, 2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methyl-indole-3-acetate (TB 219) and 2-[(2-carboxyphenoxy)carbonyl]phenyl-1-(4-chlorobenzoyl)-5- methoxy-2-methylindole-3-acetate (TB 220), were investigated in various experiments, the following results were obtained: 1. TB 219 and TB 220 showed remarkable inhibitory effects on carrageenin edema, ultraviolet erythema and adjuvant arthritis. Although TB 219 displayed almost equipotent or slightly more potent effect than those of indometacin and acemetacin, TB 220 was slightly less effective than these two reference drugs except for the therapeutic effect on adjuvant arthritis. 2. TB 219 and TB 220 inhibited the writhing syndrome induced by acetic acid and inflammatory hyperesthesia, and they provided a significant antipyretic activity. 3. Both drugs elicited almost negligible side effects in the gastrointestinal tract even after the repeated administrations. Especially, ulcerogenic activity of TB 220 was extremely weak. LD50's of both drugs are higher than that of indometacin in rats. 4. Both drugs elicited no appreciable changes in general behavior in mice and rats after oral administration. After intraperitoneal or intravenous injection of these two drugs, no marked changes in spontaneous EEG pattern and the spinal reflex were observed.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001169:Arthritis, Experimental / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects; D004064:Digestive System / Q000187:drug effects; D004487:Edema / Q000517:prevention & control; D004644:Emotions / Q000187:drug effects; D004890:Erythema / Q000517:prevention & control; D004910:Erythrocyte Membrane / Q000187:drug effects; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008297:Male; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains
D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; C049266:2-carboxyphenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate; C049267:2-((2-carboxyphenoxy)carbonyl)phenyl-1-(4-chlorobenzoyl)-5-methoxy-2-methylindole-3-acetate; D007213:Indomethacin