一氧化氮藕联的塞曲司特衍生物抗哮喘活性的研究

目的 :研究与一氧化氮供体 (NO)藕联的塞曲司特衍生物 (SDF 1、SDG 1、SDG 3)的抗哮喘活性。其中F 1为呋咱氧氮类化合物 ,G 1、G 3为羟基胍类化合物 ,SDF 1为F 1和塞曲司特连接而成的藕联化合物 ,SDG 1为G 1和塞曲司特的藕联化合物 ,SDG 3为G 3和塞曲司特的藕联化合物。方法 :以豚鼠乙酰胆碱 组胺引喘法观察其整体抗哮喘作用 ;以Griess法测定其体外NO释放量 ;以离体豚鼠气管条法测定其舒张气管作用。结果 :在 1.2 5mg·kg-1的剂量下 ,SDF 1的引喘潜伏期与塞曲司特有极显著差异 (P <0 .0 1) ,SDG 1和SDG 3与塞曲司特有显著差异 (P <0 .0 5 )。SDF 1、SDG 1体外NO释放量高于其前体药物F 1、G 1,SDG 3则低于其前体G 3。在卡巴胆碱作为收缩剂时 ,SDF 1和SDG 1舒张离体豚鼠气管平滑肌的半数有效浓度和最大舒张率均与塞曲司特及相应前体有极显著差异 (P <0 .0 1) ,SDG 3的半数有效浓度和最大舒张率与塞曲司特有极显著差异 (P <0 .0 1)。在磷酸组胺作为收缩剂时SDF 1、SDG 1和SDG 3舒张豚鼠离体气管平滑肌的半数有效浓度和最大舒张率均与塞曲司特及相应前体有极显著差异 (P <0 .0 1)。结论 :新化合物较两种前体—塞曲司特及单一的NO供体具有更强的抗哮喘活性

Study on antiasthmatic activity of seratrodast derivative connected with NO donors

AIM: To estimate the antiasthmatic activity of new compounds: SDF-1, SDG-1 and SDG-3. F-1 is a furoxan derivative, G-1 and G-3 are hydroxylguanidine derivatives, SDF-1 is a novel seratrodast derivative connected with F-1, SDG-1 a seratrodast derivative connected with G-1, and SDG-3 a novel seratrodast derivative connected with G-3. METHODS: Firstly, the in vivo antiasthmatic activity was estimated in asthmatic guinea pigs induced by acetylcholine and histamine. Secondly, the in vitro NO releasement of these compounds was determined following the procedures of Griess. Finally, tracheal smooth muscle relexant potency of these compounds was evaluated on trachea of guinea pigs. RESULTS: The in vivo antiasthmatic activity of SDF-1 was more potent than seratrodast (P< 0.01), and SDG-1 and SDG-3 were slightly more potent than seratrodast (P< 0.05). The in vitro NO releasement of SDF-1 and SDG-1 was higher than F-1 and G-1, the original compounds of SDF-1 and SDG-1, while SDG-3 was lower than its original compounds G-3. In the evaluation on trachea contracted by carbcholine, SDF-1 and SDG-1 were more potent than seratrodast, F-1 and G-1 (P< 0.01), but SDG-3 only slightly more potent than seratrodast (P< 0.01). In the evaluation on trachea contracted by histamine, SDF-1, SDG-1 and SDG-3 were slightly more potent than seratrodast and their original compounds (P< 0.01). CONCLUSION: The antiasthmatic activity of new compounds are more potent than seratrodast and their original NO donors.