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首页> 外文期刊>European Journal of Pharmacology: An International Journal >Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi
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Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi

机译：溴氰菊酯和富马酸福莫特罗对人分离支气管的相互作用的药理学表征

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Long-acting muscarinic receptor antagonists (LAMAs) and long-acting 132-adrenoceptor agonists (LABAs) cause airway smooth muscle (ASM) relaxation via different signal transduction pathways, but there are limited data concerning the interaction between these two drug classes on human bronchi. The aim of this study was to investigate the potential synergistic interaction between aclidinium bromide and formoterol fumarate on the relaxation of human ASM. We evaluated the influence of aclidinium bromide and formoterol fumarate on the contractile response induced by acetylcholine or electrical field stimulation (JPS) on human isolated airways (segmental bronchi and bronchioles). We analyzed the potential synergistic interaction between the compounds when administered in combination by using Bliss independence (BI) theory. Both aclidinium bromide and formoterol fumarate completely relaxed segmental bronchi pre-contracted with acetylcholine (E-max 97.5 +/- 2.6%, and 96.4 +/- 1.1%; pEC(50) 8.5 +/- 0.1 and 8.8 +/- 0.1; respectively). Formoterol fumarate, but not aclidinium bromide, abolished the contraction induced by acetylcholine in bronchioles 68.1 +/- 45% and 99.0 +/- 5.6%; pEC(50) 7.9 +/- 0.3 and 8.4 +/- 0.3; respectively). The BI analysis indicated synergistic interaction at low concentrations in segmental bronchi (+18.4 +/- 2.7%; P < 0.05 versus expected effect) and from low to high concentrations in bronchioles (+19.7 0.9%; P < 0.05 versus expected effect). Low concentrations of both drugs produced a synergistic relaxant interaction on isolated bronchi stimulated with EFS that was sustained for 6 h post-treatment (+551 +/- 9A%; P < 0.05 versus expected effect). These results suggest that combining acliclinium bromide plus formoterol fumarate provides synergistic benefit on ASM relaxation of both medium and small human airways, which may have major implications for the use of this combination in the clinic. (C) 2014 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license
机译：长效毒蕈碱受体拮抗剂（LAMAs）和长效132-肾上腺素受体激动剂（LABAs）通过不同的信号转导途径引起气道平滑肌（ASM）松弛，但是关于这两种药物在人支气管上的相互作用的数据有限。这项研究的目的是调查溴氰菊酯和富马酸福莫特罗之间潜在的协同相互作用对人类ASM的放松。我们评估了阿魏地溴铵和富马酸福莫特罗对乙酰胆碱或电场刺激（JPS）对人离体气道（节段性支气管和细支气管）诱导的收缩反应的影响。我们通过使用极乐独立性（BI）理论分析了组合使用时化合物之间潜在的协同相互作用。溴化阿地铵和富马酸福莫特罗均完全放松了预先用乙酰胆碱收缩的节段性支气管（E-max 97.5 +/- 2.6％和96.4 +/- 1.1％; pEC（50）8.5 +/- 0.1和8.8 +/- 0.1;分别）。富马酸福莫特罗，而不是溴化阿地铵，消除了细支气管中乙酰胆碱引起的收缩，收缩率为68.1 +/- 45％和99.0 +/- 5.6％; pEC（50）7.9 +/- 0.3和8.4 +/- 0.3;分别）。 BI分析表明，在节段性支气管中低浓度（+18.4 +/- 2.7％; P <0.05与预期效果）和细支气管中低浓度至高浓度（+19.7 0.9％; P <0.05与预期效果）具有协同作用。两种药物的低浓度在用EFS刺激的分离支气管上产生协同的松弛作用，这种作用在治疗后持续了6小时（+551 +/- 9A％;相对于预期效果，P <0.05）。这些结果表明，溴化阿昔环铵加富马酸福莫特罗联合使用对中，小型人呼吸道的ASM放松具有协同作用，这可能对该组合在临床中的使用具有重要意义。 （C）2014作者。由Elsevier B.V.发布。这是CC BY-NC-ND许可下的开放获取文章

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