Tasaka K, Kamei C, Akagi M, Mio M, Shirasaka T, Chokki M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okyama University, Japan.
Arzneimittelforschung. 1993 Dec;43(12):1331-7.
Levocabastine hydrochloride (R50 547, CAS79516-68-0) caused no inhibitory effect on the histamine release from rat peritoneal mast cells induced by compound 48/80, A23187 and concanavalin A. However, the drug inhibited histamine release from passively sensitized mast cells and passive peritoneal anaphylaxis in rats, though higher concentrations or doses were required. Moreover, levocabastine provided a relatively potent inhibitory effect on histamine release from lung pieces of actively sensitized guinea pigs exposed to antigen, and simultaneously the drug prevented a decrease in the cyclic AMP (cAMP) content. Levocabastine potently inhibited histamine-induced cutaneous reactions in rats and the drug also prevented histamine-induced contraction of isolated guinea pig ileum. Levocabastine did not induce any significant changes in platelet aggregation or in the contraction of guinea pig ileum induced by platelet activating factor (PAF). However, the drug inhibited eosinophil migration induced by PAF. The chemotaxis of neutrophils induced by N-formyl-methionyl-leucylphenylalanine (fMLP) was also inhibited by levocabastine in a dose-dependent fashion. Levocabastine has no influence on the order parameter tested with liposomes, suggesting that the drug provides no significant effect on the membrane fluidity of lipid bilayer. These results seem to indicate that the antiallergic effect of levocabastine is mainly dependent on its potent antihistaminic activity.
盐酸左卡巴斯汀（R50 547，CAS79516 - 68 - 0）对化合物48/80、A23187和伴刀豆球蛋白A诱导的大鼠腹腔肥大细胞组胺释放没有抑制作用。然而，该药物虽需要更高的浓度或剂量，但能抑制大鼠被动致敏肥大细胞的组胺释放及被动性腹膜过敏反应。此外，左卡巴斯汀对主动致敏豚鼠肺组织块暴露于抗原时的组胺释放有较强的抑制作用，同时该药物可防止环磷酸腺苷（cAMP）含量降低。左卡巴斯汀能有效抑制大鼠组胺诱导的皮肤反应，该药物还可防止组胺诱导的豚鼠离体回肠收缩。左卡巴斯汀对血小板聚集或血小板活化因子（PAF）诱导的豚鼠回肠收缩没有引起任何显著变化。然而，该药物能抑制PAF诱导的嗜酸性粒细胞迁移。左卡巴斯汀还以剂量依赖的方式抑制N - 甲酰 - 甲硫氨酰 - 亮氨酰 - 苯丙氨酸（fMLP）诱导的中性粒细胞趋化性。左卡巴斯汀对用脂质体测试的序参数没有影响，这表明该药物对脂质双层的膜流动性没有显著影响。这些结果似乎表明左卡巴斯汀的抗过敏作用主要依赖于其强大的抗组胺活性。
