Effect of inclacaterol, a novel long-acting β2-agonist, on isolated human bronchi
Effect of inclacaterol, a novel long-acting β2-agonist, on isolated human bronchi
复制标题
DOI：
10.1183/09031936.00032806
复制
发表时间：
2007-03-01
影响因子：
24.3
通讯作者：
Molimard, M.
中科院分区：
文献类型：
--
作者：
Naline, E.;Trifilieff, A.;Molimard, M.
茚达特罗是一种新型 β(2)-肾上腺素受体激动剂，正在开发中，用于每日一次治疗哮喘和慢性阻塞性肺病。本研究评估了茚达特罗对从接受肺癌手术的患者肺部获得的离体人支气管的松弛作用。在静息状态下测定效力（-logEC（50））、最大松弛作用（Emax）和起效时间。作用持续时间根据电场刺激 (EFS) 诱导的胆碱能神经收缩来确定。静息时，茚达特罗的 -logEC(50) 和 Emax 值为 8.82 +/- 0.41 和 77 +/- 5%，福莫特罗为 9.84 +/- 0.22 和 94 +/- 1%，福莫特罗为 8.36 +/- 0.16 和 74 +/- 4%对于沙美特罗，沙丁胺醇分别为 8.43 +/- 0.22 和 84 +/- 4%。与沙美特罗相反，茚达特罗不会拮抗异丙肾上腺素反应。茚达特罗的起效时间（7.8+/-0.7分钟）与福莫特罗（5.8+/-0.7分钟）或沙丁胺醇（11.0+4.0分钟）没有显着差异，但明显快于沙美特罗（19.4+/-4.3分钟）。 EFS诱导的收缩受到6.96 +/- 0.13（茚达特罗）、8.96 +/- 0.18（福莫特罗）、7.18 +/- 0.34（沙美特罗）和6.39 +/- 0.26（沙丁胺醇）的-logIC(50)值的抑制。茚达特罗和沙美特罗的作用持续时间 > 12 小时，福莫特罗和沙丁胺醇的作用持续时间分别为 35.3 +/- 8.8 和 14.6 +/- 3.7 分钟。在离体人支气管中，茚达特罗表现为长效 β(2)-肾上腺素受体激动剂，具有高内在功效和快速起效。
Indacaterol is a novel beta(2)-adrenoceptor agonist in development for the once-daily treatment of asthma and chronic obstructive pulmonary disease. The present study evaluated the relaxant effect of indacaterol on isolated human bronchi obtained from lungs of patients undergoing surgery for lung carcinoma.Potency (-logEC(50)), maximal relaxant effect (Emax) and onset of action were determined at resting tone. Duration of action was determined against cholinergic neural contraction induced by electrical field stimulation (EFS).At resting tone, -logEC(50) and Emax values were 8.82 +/- 0.41 and 77 +/- 5% for indacaterol, 9.84 +/- 0.22 and 94 +/- 1% for formoterol, 8.36 +/- 0.16 and 74 +/- 4% for salmeterol, and 8.43 +/- 0.22 and 84 +/- 4% for salbutamol, respectively.In contrast to salmeterol, indacaterol did not antagonise the isoprenaline response. Indacaterol's onset of action (7.8 +/- 0.7 min) was not significantly different from that of formoterol (5.8 +/- 0.7 min) or salbutamol (11.0+4.0 min), but it was significantly faster than that of salmeterol (19.4 +/- 4.3 min). EFS-induced contractions were inhibited with -logIC(50) values of 6.96 +/- 0.13 (indacaterol), 8.96 +/- 0.18 (formoterol), 7.18 +/- 0.34 (salmeterol) and 6.39 +/- 0.26 (salbutamol). Duration of action was > 12 h for indacaterol and salmeterol, and 35.3 +/- 8.8 and 14.6 +/- 3.7 min for formoterol and salbutamol, respectively.In isolated human bronchi, indacaterol behaved as a long-acting beta(2)-adrenoceptor agonist with high intrinsic efficacy and fast onset of action.