Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase.
SK&F 86002 [6-(4-fluorophenyl)2,3-dihydro-5-(4-pyridinyl)imidazo (2,1-b)thiazole], a dual inhibitor of arachidonic acid metabolism, administered orally to rats prevented the development of carrageenan-induced edema, immune- and nonimmune-mediated inflammation of adjuvant-induced arthritis (AA) and reduced established inflammation in AA and collagen type II-induced arthritis. A similar profile of activity was observed following treatment with the cyclooxygenase inhibitor, indomethacin. However, unlike other nonsteroidal antiinflammatory drugs, SK&F 86002 exhibited antiinflammatory activity in inflammation models that are insensitive to cyclooxygenase inhibitors such as the established inflammation in carrageenan-induced edema and the edema induced by arachidonic acid and platelet activating factor. Moreover, SK&F 86002, but not indomethacin, inhibited the immune-mediated inflammatory responses evoked in sensitized animals by challenge with purified protein derivative. In addition, SK&F 86002 produced dose-related analgesia in mice, which was not reversed by the narcotic antagonist, naltexone. SK&F 86002 thus represents an orally active antiarthritic and analgesic compound with novel antiinflammatory properties.
D000284:Administration, Oral; D000698:Analgesia; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy; D016861:Cyclooxygenase Inhibitors; D004487:Edema / Q000188:drug therapy; D007093:Imidazoles / Q000627:therapeutic use*; D016859:Lipoxygenase Inhibitors; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D013844:Thiazoles
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D016859:Lipoxygenase Inhibitors; D013844:Thiazoles; C052026:6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole