Ono N, Yamamoto N, Sunami A, Yamasaki Y, Miyake H
Nihon Yakurigaku Zasshi. 1986 Jul;88(1):33-46. doi: 10.1254/fpj.88.33.
Anti-inflammatory effects of proglumetacin maleate (PGM), a new indomethacin (IND) derivative, were compared with those of IND on an equimolar-dose basis. PGM produced a dose-dependent inhibition of vascular permeability and carrageenin edema. These inhibitory effects of PGM were greater when given 4 hr prior to phlogistic agents than when given 1 hr before. Moreover, these effects of PGM were long-acting. Inhibitory effects of PGM on kaolin edema and UV-erythema were slightly less active than those of IND. PGM markedly reduced the leukocyte migration in carrageenin pleurisy. Subacute anti-exudative and anti-granuloma effects of PGM were nearly equal to those of IND. Also, PGM showed strong prophylactic and therapeutic effects on adjuvant arthritis, the model of chronic (immuno-reactive) inflammation. These effects of PGM were superior or equal to those of IND. These pharmacological properties of PGM suggested its potential usefulness in rheumatic and other inflammatory disorders. It was considered that the mode of action of PGM mainly depended on its active metabolite, IND. However, PGM was also active in the case of local administration into the sites of inflammation on rat hind paw edema. Therefore, it seemed that PGM had a different behavior than a so called "prodrug".
将新型吲哚美辛(IND)衍生物马来酸丙谷美辛(PGM)与IND按等摩尔剂量进行比较,观察其抗炎作用。PGM对血管通透性和角叉菜胶性水肿产生剂量依赖性抑制作用。在给炎症介质前4小时给予PGM时,其抑制作用比提前1小时给药时更强。此外,PGM的这些作用具有长效性。PGM对高岭土性水肿和紫外线红斑的抑制作用略弱于IND。PGM显著减少角叉菜胶性胸膜炎中的白细胞迁移。PGM的亚急性抗渗出和抗肉芽肿作用与IND几乎相当。此外,PGM对佐剂性关节炎(慢性(免疫反应性)炎症模型)显示出强大的预防和治疗作用。PGM的这些作用优于或等同于IND。PGM的这些药理特性表明其在风湿性疾病和其他炎症性疾病中具有潜在的应用价值。据认为,PGM的作用方式主要取决于其活性代谢产物IND。然而,在大鼠后爪水肿的炎症部位进行局部给药时,PGM也具有活性。因此,PGM的行为似乎与所谓的“前体药物”不同。