吡拉米特与西拉米特的支气管扩张和抗变态反应作用比较  

Comparison of piclamilast with ciclamilast in bronchodilating and antiallergic effects

作　　者：季华[1] 谢强敏[1] 陈季强[1] 

机构地区：[1]浙江大学医学院国家食品药品监督管理局浙江呼吸药物研究实验室,浙江杭州310031

出　　处：《浙江大学学报（医学版）》2003年第4期274-278,共5页Journal of Zhejiang University(Medical Sciences)

基　　金：国家自然科学基金项目 (39970 85 7);国家重点科技 (攻关 )项目 (96 - 90 1- 0 5 - 2 6 9)

摘　　要：目的 :观察第二代磷酸二酯酶 4 (PDE4 )选择性抑制剂吡拉米特 (piclamilast)和西拉米特 (ciclamilast)对离体气管平滑肌的支气管扩张作用和抗变态反应作用 ,比较它们的作用强度。方法 :采用离体豚鼠气管片 ,蓄积剂量法评价 piclamilast和 ciclamilast对平滑肌静息张力和氨甲酰胆碱 (CCh)所致高张力的松弛作用 ,以及它们对异丙肾上腺素 (ISO)的协同作用 ;用生物检定法评价两者对致敏豚鼠肺组织抗原攻击释放过敏性慢反应物质 (SRS-A)的抑制作用 ;以及用 Schultz- Dale法评价两者对致敏豚鼠气管片抗原攻击所致收缩的抑制作用。结果 :piclami-last和 ciclamilast对静息张力气管平滑肌均有直接松弛作用 ,EC50 分别为 :piclamilast1.0 0× 10 -5mol/ L,ciclami-last 0 .84× 10 -5mol/ L ;对 CCh所致收缩无明显松弛作用 ,但都能协同 ISO的舒张作用 ,并能有效减少抗原攻击致敏豚鼠肺组织 SRS- A释放量 ,明显抑制致敏豚鼠气管 Schultz- Dale反应。结论 :结果显示 ,虽然 piclamilast和 cic-lamilast的支气管扩张作用强度相同 ,但 ciclamilast抗变态反应性作用明显强于Objective: To compare the bronchodilating and antiallergic effects of piclamilast with ciclamilast,the second-generation phosphodiesterase 4(PDE4) selective inhibitors. Methods:Effects of piclamilast and ciclamilast on airway smooth muscle(ASM) at resting tension,carbachol-induced contraction and the synergistic effect of two agents on isoproterenol-induced bronchorelaxation were evaluated in the isolated tracheal strips of guinea pig in a cumulative manner in vitro. Slow reaction substance of anaphylaxis(SRS-A) release from lung tissues of the sensitized guinea pigs after antigen challenge was examined by bioassay. Antiallergic effect of piclamilast,ciclamilast and rolipram on the isolated ASM of sensitized guinea pigs was evaluated with Schultz-Dale reaction. Results:Piclamilast and ciclamilast showed bronchorelaxant effect in ASM at resting tension. EC 50 values of piclamilast and cic-lamilast were 1.00×10 -5 mol/L and 0.84×10 -5 mol/L. Piclamilast and ciclamilast could both enhance the bronchodilating effect of isoproterenol in the isolated ASM of guinea pig,reduce the amount of SRS-A released from lung tissues of the sensitized guinea pigs and also inhibit ovalbumin(OA)-induced bronchoconstriction(Schultz-Dale reaction). Conclusion:The results indicate the bronchodilating effect of ciclamilast is as potent as piclamilast,but the antiallergic effect of ciclamilast is significantly more potent than that of piclamilast.

关 键 词：磷酸二酯酶抑制剂 异丙肾上腺素 气管/药物作用 吡拉米特 西拉米特 气管平滑肌 豚鼠 

分 类 号：R562.25[医药卫生—呼吸系统]