Pharmacology of the potent new non-steroidal anti-inflammatory agent aceclofenac.
Aceclofenac (2-[(2,6-dichlorophenyl) amine]phenylacetoxyacetic acid; CAS 89796-99-6) is a new orally effective non-steroidal anti-inflammatory agent of the phenylacetic acid group which showed remarkable anti-inflammatory, analgesic, and antipyretic properties. Hence, aceclofenac possesses a potent inhibitory activity in several models of acute and chronic inflammation in rodents, and resembles indometacin and diclofenac in its pharmacodynamic profile, being superior to naproxen and phenylbutazone. In addition, aceclofenac was found to be highly active against sodium urate-induced synovitis in dogs and adjuvant-induced polyarthritis in rats, both prophylactically and therapeutically. The analgesic effect of aceclofenac on the pain elicited by chemical and mechanical stimuli was nearly equal to or slightly better than that of indometacin and diclofenac. Fever induced by brewer's yeast injection in rats was also markedly suppressed by aceclofenac. In contrast, the acute gastric ulcerogenic activity of aceclofenac was about 2, 4 and 7-fold lesser than that of naproxen, diclofenac, or indometacin, respectively. As a consequence of its high anti-inflammatory activity and lower potential for gastric damage aceclofenac exhibited the most favourable therapeutic ratio in comparison with indometacin, diclofenac, naproxen, and phenylbutazone. These data indicate that aceclofenac could be a potent anti-inflammatory and analgesic agent with a wide margin of safety in clinical practice.
Grau
M
M
Department of Pharmacology and Toxicology, Prodesfarma Research Center, Barcelona, Spain.
Guasch
J
J
Montero
J L
JL
Felipe
A
A
Carrasco
E
E
Juliá
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000517:prevention & control; D016227:Benzoquinones; D002199:Capillary Permeability / Q000187:drug effects; D002351:Carrageenan; D004008:Diclofenac / Q000031:analogs & derivatives* / Q000494:pharmacology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy; D005260:Female; D006099:Granuloma / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D051379:Mice; D009288:Naproxen / Q000494:pharmacology; D010146:Pain / Q000139:chemically induced; D010653:Phenylbutazone / Q000494:pharmacology; D010998:Pleurisy / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D011919:Rats, Inbred Strains; D012835:Silver Nitrate; D013276:Stomach Ulcer / Q000188:drug therapy / Q000473:pathology; D013585:Synovitis / Q000139:chemically induced / Q000188:drug therapy
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016227:Benzoquinones; D004008:Diclofenac; C029322:phenylbenzoquinone; D009288:Naproxen; D002351:Carrageenan; D012835:Silver Nitrate; D010653:Phenylbutazone; C056498:aceclofenac; D007213:Indomethacin