Effects of proglumetacin maleate and its major metabolites on allergic air pouch inflammation in rats.
The mechanism of the anti-inflammatory effect of proglumetacin maleate, a novel indomethacin derivative, was examined in vivo in an allergic air pouch inflammation model in rats. Proglumetacin maleate did not affect the volume of pouch exudate 6 h after immunological challenge, irrespective of whether it was administered orally or locally, but it caused dose-dependent inhibition 24 h after challenge. It also caused dose-dependent reduction of leukocyte migration into the pouch exudate both 6 and 24 h after challenge. It markedly decreased the prostaglandin E2 content of the pouch exudate, but tended to increase the leukotriene B4 content. The main metabolites of proglumetacin maleate, desproglumideproglumetacin maleate and indomethacin, had effects similar to those of proglumetacin maleate on these four parameters on an equimolar dose basis. Unlike these three drugs, dexamethasone decreased the leukotriene B4 content of the pouch exudate. These results suggest that the action of proglumetacin maleate is qualitatively the same as that of indomethacin in vivo; that is, it inhibits cyclo-oxygenase in inflammatory sites.
Ono
N
N
Tokushima Research Institute, Taiho Pharmaceutical Co., Ltd., Japan.
Sunami
A
A
Yamasaki
Y
Y
Yamamoto
N
N
Miyake
H
H
D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D015232:Dinoprostone; D005122:Exudates and Transudates / Q000187:drug effects; D006967:Hypersensitivity / Q000378:metabolism*; D007210:Indoleacetic Acids / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism*; D007279:Injections, Subcutaneous; D007975:Leukotriene B4 / Q000378:metabolism; D008297:Male; D011458:Prostaglandins E / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007210:Indoleacetic Acids; D011458:Prostaglandins E; D007975:Leukotriene B4; D003907:Dexamethasone; C054576:desproglumideproglumetacin; C019541:proglumetacin; D015232:Dinoprostone; D007213:Indomethacin