Fujimura H, Tsurumi K, Nozaki M, Kyuki K
Nihon Yakurigaku Zasshi. 1977 Oct;73(7):837-49.
Anti-inflammatory activity and the mode of action of TAI-284 were investigated in animal models and compared with the activities of indomethacin. TAI-28 inhibited the increased vascular permeability in rats and mice which is the primary stage of inflammatory process, but the activity was less than that of indomethacin. The compound was as active as indomethacin in inhibiting acute rat paw edema induced by carrageenin and fracture. Furthermore, in the inhibitory effects on ultraviolet erythema in guinea pigs, durable paw edema induced by mustard and wound healing in rats, TAI-284 showed the same or more potent activity than indomethacin. Therefore, TAI-284 proved to have the same anti-inflammatory activity as indomethacin. TAI-284 protected rabbits from sudden death caused by intravenous injection of arachidonic acid, but the activity was about one twentieth less than that of indomethacin. The anti-inflammatory action of TAI-284 was derived from the mode of action of non-steroidal anti-inflammatory drugs, judging from the effects on ultraviolet erythema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or thema and death by arachidonic acid. On the other hand, the compound was more potent on secondary or late stage than on primary stage of inflammation, and to some extent showed the mode of action seen with steroid antiinflammatory drugs. TAI-284 displayed marked inhibitory activity on nystatin induced paw edema in rats. It is suggested that the antinflammatory action of TAI-284 may be due to the lysosomal stabilizing effect.
在动物模型中研究了TAI - 284的抗炎活性及其作用方式,并与吲哚美辛的活性进行了比较。TAI - 284抑制了大鼠和小鼠血管通透性的增加,这是炎症过程的初级阶段,但活性低于吲哚美辛。该化合物在抑制角叉菜胶和骨折诱导的急性大鼠足肿胀方面与吲哚美辛活性相当。此外,在对豚鼠紫外线红斑、芥子诱导的持续性足肿胀以及大鼠伤口愈合的抑制作用方面,TAI - 284表现出与吲哚美辛相同或更强的活性。因此,TAI - 284被证明具有与吲哚美辛相同的抗炎活性。TAI - 284可保护兔子免受静脉注射花生四烯酸引起的猝死,但活性比吲哚美辛低约二十分之一。从对紫外线红斑和花生四烯酸所致死亡的影响判断,TAI - 284的抗炎作用源自非甾体抗炎药的作用方式。另一方面,该化合物在炎症的继发性或后期比初级阶段更有效,并且在一定程度上表现出甾体抗炎药的作用方式。TAI - 284对制霉菌素诱导的大鼠足肿胀显示出显著的抑制活性。提示TAI - 284的抗炎作用可能归因于溶酶体稳定作用。