Yamada T, Tomioka K, Mase T, Murase K
Central Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Nihon Yakurigaku Zasshi. 1991 Feb;97(2):75-84. doi: 10.1254/fpj.97.2_75.
The effects of YM-13650 on experimental animal models of cell-mediated immune responses (type IV), antibody formation and type I to type III allergic reactions were investigated. YM-13650 in the dose range of 6.3 to 100 mg/kg, p.o., inhibited the picrylchloride-induced delayed type hypersensitivity (Pc-DTH) in mice when administered during the induction and the effector phases. The compound also inhibited the Pc-DTH enhanced by the pretreatment with cyclophosphamide, and even bilateral adrenalectomy failed to reduce the inhibitory effect of the compound on Pc-DTH in mice. YM-13650 in doses of 25 and 50 mg/kg, p.o., prolonged the survival time of allogenic skin grafts in mice. However, no significant effect was observed on hapten-specific IgE and HA antibody production and PFC formation in mice in doses up to 300 mg/kg, p.o. YM-13650 inhibited the passive Arthus reaction in guinea pigs and the reversed passive Arthus reaction in rats (type III). On the other hand, YM-13650 did not show any inhibitory effect on passive cutaneous anaphylaxis in rats (type I), Forssman shock in guinea pigs (type II) and carrageenin-induced paw edema in rats. These results indicate that YM-13650 suppresses not only cell-mediated immune responses but also type III allergic reactions without any influence on type I and type II allergic reactions as well as an acute inflammatory reaction.
研究了YM - 13650对细胞介导的免疫反应(IV型)、抗体形成以及I型至III型过敏反应的实验动物模型的影响。口服剂量范围为6.3至100 mg/kg的YM - 13650,在诱导期和效应期给药时,可抑制小鼠中苦味酸氯诱导的迟发型超敏反应(Pc - DTH)。该化合物还抑制了环磷酰胺预处理增强的Pc - DTH,甚至双侧肾上腺切除也未能降低该化合物对小鼠Pc - DTH的抑制作用。口服剂量为25和50 mg/kg的YM - 13650可延长小鼠同种异体皮肤移植的存活时间。然而,口服剂量高达300 mg/kg时,未观察到对小鼠中半抗原特异性IgE和HA抗体产生以及PFC形成有显著影响。YM - 13650抑制豚鼠的被动Arthus反应和大鼠的反向被动Arthus反应(III型)。另一方面,YM - 13650对大鼠的被动皮肤过敏反应(I型)、豚鼠的福斯曼休克(II型)和大鼠角叉菜胶诱导的爪肿胀没有任何抑制作用。这些结果表明,YM - 13650不仅抑制细胞介导的免疫反应,还抑制III型过敏反应,而对I型和II型过敏反应以及急性炎症反应没有任何影响。