Matera Maria Gabriella, Cazzola Mario
Department of Experimental Medicine, Unit of Pharmacology, Second University of Naples, Naples, Italy.
Division of Respiratory Medicine, University Hospital Tor Vergata, Rome, Italy.
Handb Exp Pharmacol. 2017;237:41-62. doi: 10.1007/164_2016_68.
Parasympathetic activity is increased in patients with chronic obstructive pulmonary disease (COPD) and asthma and appears to be the major reversible component of airway obstruction. Therefore, treatment with muscarinic receptor antagonists is an effective bronchodilator therapy in COPD and also in asthmatic patients. In recent years, the accumulating evidence that the cholinergic system controls not only contraction by airway smooth muscle but also the functions of inflammatory cells and airway epithelial cells has suggested that muscarinic receptor antagonists could exert other effects that may be of clinical relevance when we must treat a patient suffering from COPD or asthma. There are currently six muscarinic receptor antagonists licenced for use in the treatment of COPD, the short-acting muscarinic receptor antagonists (SAMAs) ipratropium bromide and oxitropium bromide and the long-acting muscarinic receptor antagonists (LAMAs) aclidinium bromide, tiotropium bromide, glycopyrronium bromide and umeclidinium bromide. Concerns have been raised about possible associations of muscarinic receptor antagonists with cardiovascular safety, but the most advanced compounds seem to have an improved safety profile. Further beneficial effects of SAMAs and LAMAs are seen when added to existing treatments, including LABAs, inhaled corticosteroids and phosphodiesterase 4 inhibitors. The importance of tiotropium bromide in the maintenance treatment of COPD, and likely in asthma, has spurred further research to identify new LAMAs. There are a number of molecules that are being identified, but only few have reached the clinical development.
慢性阻塞性肺疾病（COPD）和哮喘患者的副交感神经活动增强，且似乎是气道阻塞的主要可逆成分。因此，使用毒蕈碱受体拮抗剂进行治疗在COPD患者以及哮喘患者中都是一种有效的支气管扩张疗法。近年来，越来越多的证据表明胆碱能系统不仅控制气道平滑肌的收缩，还控制炎症细胞和气道上皮细胞的功能，这表明当我们治疗COPD或哮喘患者时，毒蕈碱受体拮抗剂可能会发挥其他具有临床意义的作用。目前有六种毒蕈碱受体拮抗剂被批准用于治疗COPD，短效毒蕈碱受体拮抗剂（SAMA）异丙托溴铵和氧托溴铵，以及长效毒蕈碱受体拮抗剂（LAMA）阿地溴铵、噻托溴铵、格隆溴铵和乌美溴铵。人们对毒蕈碱受体拮抗剂与心血管安全性之间可能存在的关联表示担忧，但最先进的化合物似乎具有更好的安全性。当SAMA和LAMA添加到包括长效β2受体激动剂（LABA）、吸入性糖皮质激素和磷酸二酯酶4抑制剂在内的现有治疗中时，可观察到进一步的有益效果。噻托溴铵在COPD维持治疗以及可能在哮喘维持治疗中的重要性，促使人们进一步开展研究以寻找新的LAMA。目前正在鉴定许多分子，但只有少数进入了临床开发阶段。
