Massó J M, Villar A M, Conde J R, Martorell J
Department of Pharmacology, Elmu S.A., Arganda del Rey, Madrid, Spain.
Arzneimittelforschung. 1994 Jan;44(1):68-74.
The mechanism of the anti-inflammatory activity of fepradinol (CAS 67704-50-1) has been investigated. The effect of fepradinol was compared with that of indometacin and other non-steroidal anti-inflammatory drugs. Oral dosing of fepradinol and cyproheptadine suppressed zymosan-induced paw edema in rats. Indometacin and piroxicam were without effect. Fepradinol inhibited the early and late stages of concanavalin A-induced edema in rats; indometacin and piroxicam only inhibited the late stage. Fepradinol and indometacin prevented the carrageenin-induced inflammation in rats: they acted on the exudate, on the increase of protein and gamma-glutamyltransferase levels, and also reduced the number of leucocytes. But, in contrast to indometacin, fepradinol did not inhibit prostaglandin E2 biosynthesis. Fepradinol and indometacin prevented diarrhoea induced by intravenous injection of endotoxin in mice or by oral administration of castor oil in rats. In in vitro tests, fepradinol did not inhibit prostaglandin biosynthesis from arachidonic acid by bovine seminal vesicle microsomal enzyme or 15-lipoxygenase. These results indicate that fepradinol possesses a potent inhibitory activity on the acute inflammation in rodents and that its anti-inflammatory activity does not seem to be related to an inhibitory effect on prostaglandin biosynthesis.
已对非普拉地诺（化学物质登记号67704 - 50 - 1）的抗炎活性机制进行了研究。将非普拉地诺的效果与吲哚美辛及其他非甾体抗炎药的效果进行了比较。给大鼠口服非普拉地诺和赛庚啶可抑制酵母聚糖诱导的爪部水肿。吲哚美辛和吡罗昔康则无此作用。非普拉地诺可抑制大鼠因刀豆蛋白A诱导的水肿的早期和晚期阶段；吲哚美辛和吡罗昔康仅抑制晚期阶段。非普拉地诺和吲哚美辛可预防大鼠角叉菜胶诱导的炎症：它们作用于渗出物、蛋白质和γ - 谷氨酰转移酶水平的升高，还减少了白细胞数量。但是，与吲哚美辛不同，非普拉地诺不抑制前列腺素E2的生物合成。非普拉地诺和吲哚美辛可预防小鼠静脉注射内毒素或大鼠口服蓖麻油诱导的腹泻。在体外试验中，非普拉地诺不抑制牛精囊微粒体酶或15 - 脂氧合酶由花生四烯酸合成前列腺素。这些结果表明，非普拉地诺对啮齿动物的急性炎症具有强效抑制活性，且其抗炎活性似乎与对前列腺素生物合成的抑制作用无关。
