Comparison of bronchodilating and antiinflammatory activities of oral formoterol and its (R,R)-enantiomers  

口服福莫特罗与其(R,R)对映体的支气管扩张和抗炎活性比较(英文)

作　　者：谢强敏[1] 陈季强[1] 沈文会[1] 杨秋火[1] 卞如濂[1] 

机构地区：[1]浙江大学医学院国家药品监督管理局浙江呼吸药物研究实验室

出　　处：《Acta Pharmacologica Sinica》2003年第3期277-282,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China, № 39970857.

摘　　要：AIM: To compare the bronchodilating and antiinflammatory effects of oral racemic formoterol (rac-FMT) and (R, R)-formoterol (R,R-FMT). METHODS: The changes of lung resistance (R_L), dynamic lung compliance (C_(dyn)), and the accumulation of inflammatory cells in bronchoalveolar lavage fluids (BALF) induced by ovalbumin aerosol in sensitized guinea pigs and mice were investigated in vivo. RESULTS: Mean value increase of RL and mean value reduction of C_(dyn) from 1 to 30 min after antigen challenge were up to 101%±34% and 42%±7%, respectively. rac-FMT 0.5, 1.0, and 2.0 mg/kg, and R,R-FMT 0.25, 0.5, and 1.0mg/kg ig, induced dose-related inhibition of the bronchoconstrictive responses to aerosolised ovalbumin. ID_(50)(95% confidence limits, 95% CL) value of rac-FMT on R_L maximal increase and C_(dyn) maximal reduction at 5 min were 0.64 (0.54-0.76) and 1.02(0.88-1.18) mg/kg, respectively. For R,R-FMT they were 0.46 (0.40-0.53) and 0.52 (0.45-0.61) mg/kg, respectively. ID_(50) (95% CL) value of rac-FMT on R_L mean increase and C_(dyn) mean reduction from 1 to 30 min were 0.96 (0.86-1.07) and 1.59 (1.32-1.92) mg/kg, respectively. For R,R-FMT they were 0.52 (0.45-0.59) and 0.43 (0.37-0.51) mg/kg, respectively. Ovalbumin-aerosol challenge induced an increase of inflammatory cells in BALF in sensitized mice. rac-FMT and RR-FMT caused a dose-dependent and almost complete inhibition at 2.0 mg/kg. ID(50) (95% CL) of rac-FMT on the number of total inflammatory cells and eosinophil in BALF were 1.48 (1.22-1.81) and 0.80 (0.62-1.04) mg/kg, respectively. ID_(50) (95% CL) of RR-FMT were 0.80 (0.57-1.13) and 0.60 (0.43-0.83) mg/kg, respectively. CONCLUSION: R,R-FMT protected lung against increase of R_L and reduction of C_(dyn) induced by bronchial challenge of ovalbumin in the asthma model of guinea pigs, and inhibited airway inflammation in the sensitized mice. Efficacy of R,R-FMT was approximately 2-fold than that of rac-FMT.目的:比较口服福莫特罗(rac-FMT)和(R,R)-福莫特罗(R,R-FMT)的支气管扩张和抗炎作用。方法:分别采用抗原气雾攻击致敏豚鼠和小鼠,观察豚鼠的肺功能变化以及小鼠肺内炎症细胞的集聚反应。结果:模型组豚鼠在抗原激发后1-30min的气道阻力(R_L)平均值增加101％±34％,动态肺顺应性(C_(dyn))降低42％±7％。rac-FMT 0.5,1.0和2.0 mg/g,R,R-FMT 0.25,0.5和1.0mg/kg灌胃给药(ig)呈剂量依赖抑制抗原引起的支气管收缩反应,rac-FMT的ID_(50)(95％可信限)分别为0.96(0.86-1.07)和1.59(1.32-1.92)mg/g;R,R-FMT分别为0.52(0.45-0.59)和0.43(0.37-0.51)mg/g。rac-FMT抑制抗原攻击引起的致敏小鼠肺内总炎症细胞和嗜 酸性粒细胞聚集,ID_(50)(95％C1)分别为1.48(1.22-1.81)和0.80(0.62-1.04)mg/g;RR-FMT分别为0.80(0.57-1.13)和0.60(0.43-0.83)mg/g。结论:R,R-FMT保护豚鼠哮喘模型抗原攻击引起的R_1和C_(dyn)变化,抑制致敏小鼠的气道炎症,其作用强于rac-FMT约2倍。

关 键 词：FORMOTEROL bronchodilator agents inflammation EOSINOPHILS ASTHMA guinea pigs mice 

分 类 号：R96[医药卫生—药理学]