Oxaceprol, an atypical inhibitor of inflammation and joint damage.
Oxaceprol, an established therapeutic agent for osteoarthritis, had no effect on macrophage prostaglandin E2 release in vitro and inhibited carrageenan paw oedema at high doses (18-150 mg/kg p.o.). In the same dose range, oxaceprol was comparable to indomethacin (3 mg/kg p.o.) as an inhibitor of yeast hyperalgaesia and at 6-50 mg/kg/day p.o. had a mild, variable inhibitory effect on cotton pellet granuloma formation. In adjuvant arthritic rats, oxaceprol (6-54 mg/kg/day p.o.) given therapeutically had no effect on the primary paw oedema response, but inhibited secondary lesions in the ears and tail. Histologically, oxaceprol markedly inhibited inflammatory cell infiltration and bone damage in the adjuvant-injected paw. In contrast to indomethacin, oxaceprol was more effective at inhibiting periarticular soft tissue inflammation but did not affect cartilage breakdown in this model. Oxaceprol has a clearly different spectrum of action to NSAIDs such as indomethacin and may act by inhibiting leucocyte infiltration and late connective tissue changes during inflammatory joint disease.
Ionac
M
M
Institute for Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Parnham
M J
MJ
Plauchithiu
M
M
Brune
K
K
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000473:pathology*; D002351:Carrageenan; D015232:Dinoprostone / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D015777:Eicosanoids / Q000378:metabolism; D006099:Granuloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006909:Hydroxyproline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006930:Hyperalgesia / Q000188:drug therapy; D007213:Indomethacin / Q000494:pharmacology; D007596:Joints / Q000473:pathology*; D017997:Leukotriene C4 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D017997:Leukotriene C4; D002351:Carrageenan; D015232:Dinoprostone; C012393:oxaceprol; D006909:Hydroxyproline; D007213:Indomethacin