Abstract
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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Annis P, Landa J, Lichtiger M (1976) Effects of atropine on velocity of tracheal mucus in anesthetized patients. Anesthesiology 44:74–77
Arai N, Kondo M, Izumo T, Tamaoki J, Nagai A (2010) Inhibition of neutrophil elastase-induced goblet cell metaplasia by tiotropium in mice. Eur Respir J 35:1164–1171. doi:10.1183/09031936.00040709
Asano K, Shikama Y, Shibuya Y, Nakajima H, Kanai K, Yamada N et al (2008) Suppressive activity of tiotropium bromide on matrix metalloproteinase production from lung fibroblasts in vitro. Int J Chron Obstruct Pulmon Dis 3:781–789
Asano K, Shikama Y, Shoji N, Hirano K, Suzaki H, Nakajima H (2010) Tiotropium bromide inhibits TGF-β-induced MMP production from lung fibroblasts by interfering with Smad and MAPK pathways in vitro. Int J Chron Obstruct Pulmon Dis 5:277–286
Barnes P (2004) Distribution of receptor targets in the lung. Proc Am Thorac Soc 1:345–351
Bennett WD, Chapman WF, Mascarella JM (1993) The acute effect of ipratropium bromide bronchodilator therapy on cough clearance in COPD. Chest 103:488–495
Birrell MA, Bonvini SJ, Dubuis E, Maher SA, Wortley MA, Grace MS et al (2014) Tiotropium modulates transient receptor potential V1 (TRPV1) in airway sensory nerves: A beneficial off-target effect? J Allergy Clin Immunol 133:679–687. doi:10.1016/j.jaci.2013.12.003
Bjermer L, Bengtsson T, Jorup C, Lötvall J (2013) Local and systemic effects of inhaled AZD9164 compared with tiotropium in patients with COPD. Respir Med 107:84–90. doi:10.1016/j.rmed.2012.09.014
Bos I, Gosens R, Zuidhof A, Schaafsma D, Halayko AJ, Meurs H et al (2007) Inhibition of allergen-induced airway remodelling by tiotropium and budesonide: a comparison. Eur Respir J 30:653–661. doi:10.1183/09031936.00004907
Buels KS, Fryer AD (2012) Muscarinic receptor antagonists: effects on pulmonary function. Handb Exp Pharmacol 208:317–341. doi:10.1007/978-3-642-23274-9_14
Buels K, Jacoby D, Fryer A (2012) Non-bronchodilating mechanisms of tiotropium prevent airway hyperreactivity in a guinea pig model of allergic asthma. Br J Pharmacol 165:1501–1514. doi:10.1111/j.1476-5381.2011.01632.x
Buhl R, Banerji D (2012) Profile of glycopyrronium for once-daily treatment of moderate-to-severe COPD. Int J Chron Obstruct Pulmon Dis 7:729–741. doi:10.2147/COPD.S36001
Buhling F, Lieder N, Kuhlmann UC, Waldburg N, Welte T (2007) Tiotropium suppresses acetylcholine-induced release of chemotactic mediators in vitro. Respir Med 101:2386–2394
Casaburi R, Briggs DD, Donohue JF, Serby CW, Menjoge SS, Witek TJ Jr (2000) The spirometric efficacy of once-daily dosing with tiotropium in stable COPD. Chest 118:1294–1302
Cazzola M, Matera MG (2014a) Bronchodilators: current and future. Clin Chest Med 35:191–201. doi:10.1016/j.ccm.2013.10.005
Cazzola M, Matera MG (2014b) Triple combinations in chronic obstructive pulmonary disease - is three better than two? Expert Opin Pharmacother 15:2475–2478. doi:10.1517/14656566.2014.972367
Cazzola M, Molimard M (2010) The scientific rationale for combining long-acting beta2-agonists and muscarinic antagonists in COPD. Pulm Pharmacol Ther 23:257–267. doi:10.1016/j.pupt.2010.03.003
Cazzola M, Centanni S, Donner CF (1998a) Anticholinergic agents. Pulm Pharmacol Ther 11:381–392
Cazzola M, Matera MG, Di Perna F, Calderaro F, Califano C, Vinciguerra A (1998b) A comparison of bronchodilating effects of salmeterol and oxitropium bromide in stable chronic obstructive pulmonary disease. Respir Med 92:354–357. doi:10.1016/S0954-6111(98)90121-4
Cazzola M, Page CP, Calzetta L, Matera MG (2012a) Pharmacology and therapeutics of bronchodilators. Pharmacol Rev 64:450–504. doi:10.1124/pr.111.004580
Cazzola M, Rogliani P, Segreti A, Matera MG (2012b) An update on bronchodilators in Phase I and II clinical trials. Expert Opin Investig Drugs 21:1489–1501. doi:10.1517/13543784.2012.710602
Cazzola M, Page C, Matera MG (2013a) Long-acting muscarinic receptor antagonists for the treatment of respiratory disease. Pulm Pharmacol Ther 26:307–317. doi:10.1016/j.pupt.2012.12.006
Cazzola M, Page CP, Matera MG (2013b) Aclidinium bromide for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother 14:1205–1214. doi:10.1517/14656566.2013.789021
Cazzola M, Calzetta L, Page CP, Rogliani P, Facciolo F, Gavaldà A et al (2014) Pharmacological characterization of the interaction between aclidinium bromide and formoterol fumarate on human isolated bronchi. Eur J Pharmacol 745:135–143. doi:10.1016/j.ejphar.2014.10.025
Cazzola M, Calzetta L, Segreti A, Facciolo F, Rogliani P, Matera MG (2015a) Translational study searching for synergy between glycopyrronium and indacaterol. COPD 12:175–181. doi:10.3109/15412555.2014.922172
Cazzola M, Beeh KM, Price D, Roche N (2015b) Assessing the clinical value of fast onset and sustained duration of action of long-acting bronchodilators for COPD. Pulm Pharmacol Ther 31:68–78. doi:10.1016/j.pupt.2015.02.007
Cazzola M, Calzetta L, Matera MG (2015c) Aclidinium/formoterol fixed-dose combination for the treatment of chronic obstructive pulmonary disease. Drugs Today (Barc) 51:97–105. doi:10.1358/dot.2015.51.2.2273382
Celli B, Decramer M, Leimer I, Vogel U, Kesten S, Tashkin DP (2010) Cardiovascular safety of tiotropium in patients with COPD. Chest 137:20–30. doi:10.1378/chest.09-0011
Choi J, Na J, Kim Y (2007) The effect of tiotropium and inhaled corticosteroid combination therapy in chronic obstructive pulmonary disease (COPD) and chronic obstructive bronchial asthma (COBA) associated with irreversible pulmonary function [abstract]. Am J Respir Crit Care Med 175:A130
Chong J, Karner C, Poole P (2012) Tiotropium versus long-acting beta-agonists for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 9:CD009157. doi:10.1002/14651858.CD009157.pub2
Chung KF (2015) Tiotropium as an add-on therapy in patients with symptomatic asthma. Lancet Respir Med. doi:10.1016/S2213-2600(15)00039-9
Compton C, McBryan D, Bucchioni E, Patalano F (2013) The Novartis view on emerging drugs and novel targets for the treatment of chronic obstructive pulmonary disease. Pulm Pharmacol Ther 26:562–573. doi:10.1016/j.pupt.2013.05.009
Cope S, Donohue JF, Jansen JP, Kraemer M, Capkun-Niggli G, Baldwin M et al (2013) Comparative efficacy of long-acting bronchodilators for COPD – a network meta-analysis. Respir Res 14:100. doi:10.1186/1465-9921-14-100
Cortijo J, Mata M, Milara J, Donet E, Gavaldà A, Miralpeix M et al (2011) Aclidinium inhibits cholinergic and tobacco smoke-induced MUC5AC in human airways. Eur Respir J 37:244–254. doi:10.1183/09031936.00182009
Damera G, Jiang M, Zhao H, Fogle HW, Jester WF, Freire J et al (2010) Aclidinium bromide abrogates allergen-induced hyperresponsiveness and reduces eosinophilia in murine model of airway inflammation. Eur J Pharmacol 649:349–353. doi:10.1016/j.ejphar.2010.09.043
Dicpinigaitis P, Spinner L, Santhyadka G, Negassa A (2008) Effect of tiotropium on cough reflex sensitivity in acute viral cough. Lung 186:369–374. doi:10.1007/s00408-008-9114-6
Domínguez-Fandos D, Ferrer E, Puig-Pey R, Carreño C, Prats N, Aparici M et al (2014) Effects of aclidinium bromide in a cigarette smoke-exposed guinea pig model of COPD. Am J Respir Cell Mol Biol 50:337–346. doi:10.1165/rcmb.2013-0117OC
Dong YH, Lin HH, Shau WY, Wu YC, Chang CH, Lai MS (2013) Comparative safety of inhaled medications in patients with chronic obstructive pulmonary disease; systematic review and mixed treatment comparison meta-analysis of randomised controlled trials. Thorax 68:48–56. doi:10.1136/thoraxjnl-2012-201926
Donohue JF, van Noord JA, Bateman ED, Langley SJ, Lee A, Witek TJ Jr et al (2002) A 6-month, placebo-controlled study comparing lung function and health status changes in COPD patients treated with tiotropium or salmeterol. Chest 122:47–55. doi:10.1378/chest.122.1.47
Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ et al (2009) Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with long acting bronchodilators: two randomised clinical trials. Lancet 374:695–703. doi:10.1016/S0140-6736(09)61252-6
Global Initiative for Chronic Obstructive Lung Disease (GOLD) (2014) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. http://www.goldcopd.org/guidelines-global-strategy-for-diagnosis-management.html
Gosens R, Bos I, Zaagsma J, Meurs H (2005) Protective effects of tiotropium bromide in the progression of airway smooth muscle remodeling. Am J Respir Crit Care Med 171:1096–1102. doi:10.1164/rccm.200409-1249OC
Griffiths B, Ducharme FM (2013) Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev 8:CD000060. doi:10.1002/14651858.CD000060.pub2
Gross NJ (2006) Anticholinergic agents in asthma and COPD. Eur J Pharmacol 533:36–39. doi:10.1016/j.ejphar.2005.12.072
Gross NJ, Skorodin MS (1984) Role of the parasympathetic system in airway obstruction due to emphysema. N Engl J Med 311:421–425. doi:10.1056/NEJM198408163110701
Haag S, Matthiesen S, Juergens UR, Racke K (2008) Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J 32:555–562. doi:10.1183/09031936.00129307
Halpin DM, Dahl R, Hallmann C, Mueller A, Tashkin D (2015) Tiotropium HandiHaler® and Respimat® in COPD: a pooled safety analysis. Int J Chron Obstruct Pulmon Dis 10:239–259. doi:10.2147/COPD.S75146
Hasani A, Toms N, Agnew JE, Sarno M, Harrison AJ, Dilworth P (2004) The effect of inhaled tiotropium bromide on lung mucociliary clearance in patients with COPD. Chest 125:1726–1734
Holmes PW, Barter CE, Pierce RJ (1992) Chronic persistent cough: use of ipratropium bromide in undiagnosed cases following upper respiratory tract infection. Respir Med 86:425–429
Hoshino M, Ohtawa J (2013) Effects of tiotropium and salmeterol/fluticasone propionate on airway wall thickness in chronic obstructive pulmonary disease. Respiration 86:280–287. doi:10.1159/000351116
Ishihara H, Shimura S, Satoh M, Masuda T, Nonaka H, Kase H et al (1992) Muscarinic receptor subtypes in feline tracheal submucosal gland secretion. Am J Physiol 262:L223–L228
Jacoby DB, Yost BL, Kumaravel B, Chan-Li Y, Xiao HQ, Kawashima K et al (2001) Glucocorticoid treatment increases inhibitory m2 muscarinic receptor expression and function in the airways. Am J Respir Cell Mol Biol 24:485–491. doi:10.1165/ajrcmb.24.4.4379
Jones P (2013) Aclidinium bromide twice daily for the treatment of chronic obstructive pulmonary disease: a review. Adv Ther 30:354–368. doi:10.1007/s12325-013-0019-2
Jorup C, Bengtsson T, Strandgården K, Sjöbring U (2014) Transient paradoxical bronchospasm associated with inhalation of the LAMA AZD9164: analysis of two Phase I, randomised, double-blind, placebo-controlled studies. BMC Pulm Med 14:52. doi:10.1186/1471-2466-14-52
Kang JY, Rhee CK, Kim JS, Park CK, Kim SJ, Lee SH et al (2012) Effect of tiotropium bromide on airway remodeling in a chronic asthma model. Ann Allergy Asthma Immunol 109:29–35. doi:10.1016/j.anai.2012.05.005
Karner C, Chong J, Poole P (2012) Tiotropium versus placebo for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 7:CD009285. doi:10.1002/14651858.CD009285.pub2
Keating GM (2012) Tiotropium bromide inhalation powder: a review of its use in the management of chronic obstructive pulmonary disease. Drugs 72:273–300. doi:10.2165/11208620-000000000-00000
Kerstjens HA, Engel M, Dahl R, Paggiaro P, Beck E, Vandewalker M et al (2012) Tiotropium in asthma poorly controlled with standard combination therapy. N Engl J Med 367:1198–1207. doi:10.1056/NEJMoa1208606
Kerstjens HA, Casale TB, Bleecker ER, Meltzer EO, Pizzichini E, Schmidt O et al (2015) Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir Med. doi:10.1016/S2213-2600(15)00031-4
Kistemaker LE, Gosens R (2015) Acetylcholine beyond bronchoconstriction: roles in inflammation and remodeling. Trends Pharmacol Sci 36:164–171. doi:10.1016/j.tips.2014.11.005
Kruse AC, Hu J, Kobilka BK, Wess J (2014) Muscarinic acetylcholine receptor X-ray structures: potential implications for drug development. Curr Opin Pharmacol 16:24–30. doi:10.1016/j.coph.2014.02.006
Lee TA, Pickard AS, Au DH, Bartle B, Weiss KB (2008) Risk for death associated with medications for recently diagnosed chronic obstructive pulmonary disease. Ann Intern Med 149:380–390. doi:10.7326/0003-4819-149-6-200809160-00004
Lee LA, Briggs A, Edwards LD, Yang S, Pascoe S (2015a) A randomized, three-period crossover study of umeclidinium as monotherapy in adult patients with asthma. Respir Med 109:63–73. doi:10.1016/j.rmed.2014.10.009
Lee LA, Yang S, Kerwin E, Trivedi R, Edwards LD, Pascoe S (2015b) The effect of fluticasone furoate/umeclidinium in adult patients with asthma: A randomized, dose-ranging study. Respir Med 109:54–62. doi:10.1016/j.rmed.2014.09.012
Lips KS, Brüggmann D, Pfeil U, Vollerthun R, Grando SA, Kummer W (2005) Nicotinic acetylcholine receptors in rat and human placenta. Placenta 26:735–746, http://dx.doi.org/10.1016/j.placenta.2004.10.009
Lipworth BJ (2014) Emerging role of long acting muscarinic antagonists for asthma. Br J Clin Pharmacol 77:55–62. doi:10.1111/bcp.12123
Lougheed MD, Lemière C, Dell SD, Ducharme FM, Fitzgerald JM, Leigh R et al (2010) Canadian Thoracic Society Asthma Management Continuum--2010 Consensus Summary for children six years of age and over, and adults. Can Respir J 17:15–24
Lowry R, Wood A, Johnson T, Higenbottam T (1988) Antitussive properties of inhaled bronchodilators on induced cough. Chest 93:1186–1189. doi:10.1378/chest.93.6.1186
Lowry R, Wood A, Higenbottam T (1994) The effect of anticholinergic bronchodilator therapy on cough during upper respiratory tract infections. Br J Clin Pharmacol 37:187–191
Mahler DA, D'Urzo A, Bateman ED, Ozkan SA, White T, Peckitt C et al (2012) Concurrent use of indacaterol plus tiotropium in patients with COPD provides superior bronchodilation compared with tiotropium alone: a randomised, double-blind comparison. Thorax 67:781–788. doi:10.1136/thoravxjnl-2011-201140
Manickam R, Asija A, Aronow WS (2014) Umeclidinium for treating COPD: an evaluation of pharmacologic properties, safety and clinical use. Expert Opin Drug Saf 13:1555–1561. doi:10.1517/14740338.2014.968550
Manoharan A, Short PM, Anderson WJ, Lipworth BJ (2014) Impact of long-acting bronchodilators and exposure to inhaled corticosteroids on mortality in COPD: a real-life retrospective cohort study. Lung 192:649–652. doi:10.1007/s00408-014-9611-8
Matera MG, Cazzola M, Vinciguerra A, Di Perna F, Calderaro F, Caputi M et al (1995) A comparison of the bronchodilating effects of salmeterol, salbutamol and ipratropium bromide in patients with chronic obstructive pulmonary disease. Pulm Pharmacol 8:267–271
Matera MG, Page CP, Cazzola M (2011) Novel bronchodilators for the treatment of chronic obstructive pulmonary disease. Trends Pharmacol Sci 32:495–506. doi:10.1016/j.tips.2011.04.003
Matera MG, Rogliani P, Cazzola M (2014) Muscarinic receptor antagonists for the treatment of chronic obstructive pulmonary disease. Expert Opin Pharmacother 15:961–977. doi:10.1517/14656566.2014.899581
Matera MG, Rogliani P, Rinaldi B, Cazzola M (2015a) Umeclidinium bromide + vilanterol for the treatment of chronic obstructive pulmonary disease. Expert Rev Clin Pharmacol 8:35–41. doi:10.1586/17512433.2015.977256
Matera MG, Rogliani P, Cazzola M (2015b) QVA149 (indacaterol/glycopyrronium) for the treatment of COPD. Expert Opin Pharmacother. doi:10.1517/14656566.2015.1032247
Meurs H, Dekkers BG, Maarsingh H, Halayko AJ, Zaagsma J, Gosens R (2013a) Muscarinic receptors on airway mesenchymal cells: novel findings for an ancient target. Pulm Pharmacol Ther 26:145–155. doi:10.1016/j.pupt.2012.07.003
Meurs H, Oenema TA, Kistemaker LE, Gosens R (2013b) A new perspective on muscarinic receptor antagonism in obstructive airways diseases. Curr Opin Pharmacol 13:316–323. doi:10.1016/j.coph.2013.04.004
Milara J, Serrano A, Peiro T et al (2012) Aclidinium inhibits human lung fibroblast to myofibroblast transition. Thorax 67:229–237. doi:10.1136/thoraxjnl-2011-200376
Milara J, Serrano A, Peiró T, Artigues E, Gavaldà A, Miralpeix M et al (2013) Aclidinium inhibits cigarette smoke-induced lung fibroblast-to-myofibroblast transition. Eur Respir J 41:1264–1274. doi:10.1183/09031936.00017712
Miyata T, Matsumoto N, Yuki H et al (1989) Effects of anticholinergic bronchodilators on mucociliary transport and airway secretion. Jpn J Pharmacol 51:11–15
Morcillo E, Cortijo J (2006) Mucus and MUC in asthma. Curr Opin Pulm Med 12:1–6
Ni H, Soe Z, Moe S (2014) Aclidinium bromide for stable chronic obstructive pulmonary disease. Cochrane Database Syst Rev 9:CD010509. doi:10.1002/14651858.CD010509.pub2
Ohta S, Oda N, Yokoe T, Tanaka A, Yamamoto Y, Watanabe Y et al (2010) Effect of tiotropium bromide on airway inflammation and remodelling in a mouse model of asthma. Clin Exp Allergy 40:1266–1275. doi:10.1111/j.1365-2222.2010.03478.x
Orevillo C, St Rose E, Strom S, Fischer T, Golden M, Thomas M et al (2011) Glycopyrrolate MDI demonstrates comparable efficacy and safety to tiotropium DPI in a randomised, double-blind, placebo-controlled phase 2b study in patients with COPD [abstract]. Eur Respir J 38(Suppl 55):724s
Pahl A, Bauhofer A, Petzold U, Cnota PJ, Maus J, Brune K et al (2006) Synergistic effects of the anti-cholinergic R, R-glycopyrrolate with anti-inflammatory drugs. Biochem Pharmacol 72:1690–1696. doi:10.1016/j.bcp.2006.07.025
Pera T, Penn RB (2014) Crosstalk between beta-2-adrenoceptor and muscarinic acetylcholine receptors in the airway. Curr Opin Pharmacol 16:72–81. doi:10.1016/j.coph.2014.03.005
Pera T, Zuidhof A, Valadas J, Smit M, Schoemaker RG, Gosens R et al (2011) Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J 38:789–796. doi:10.1183/09031936.00146610
Peters SP, Bleecker ER, Kunselman SJ, Icitovic N, Moore WC, Pascual R et al (2013) Predictors of response to tiotropium versus salmeterol in asthmatic adults. J Allergy Clin Immunol 132:1068–1074. doi:10.1016/j.jaci.2013.08.003
Pieper MP, Chaudhary NI, Park JE (2007) Acetylcholine-induced proliferation of fibroblasts and myofibroblasts in vitro is inhibited by tiotropium bromide. Life Sci 80:2270–2273
Potgieter P, Hopkins A, Liu P et al (2012) A randomized, crossover study to examine the pharmacodynamics and safety of a new antimuscarinic (TD-4208) in COPD (Abstract). Eur Respir J 40(Suppl 56):2878
Powrie DJ, Wilkinson TMA, Donaldson GC, Jones P, Scrine K, Viel K et al (2007) Effect of tiotropium on sputum and serum inflammatory markers and exacerbations of COPD. Eur Respir J 30:472–478. doi:10.1183/09031936.00023907
Price D, Fromer L, Kaplan A, van der Molen T, Román-Rodríguez M (2014) Is there a rationale and role for long-acting anticholinergic bronchodilators in asthma? NPJ Prim Care Respir Med 24:14023. doi:10.1038/npjpcrm.2014.23
Profita M, Giorgi RD, Sala A, Bonanno A, Riccobono L, Mirabella F et al (2005) Muscarinic receptors, leukotriene B4 production and neutrophilic inflammation in COPD. Allergy 60:1361–1369. doi:10.1111/j.1398-9995.2005.00892.x
Profita M, Riccobono L, Montalbano AM, Bonanno A, Ferraro M, Albano GD et al (2012) In vitro anticholinergic drugs affect CD8+ peripheral blood T-cells apoptosis in COPD. Immunobiology 217:345–353. doi:10.1016/j.imbio.2011.07.013
Ramnarine S, Haddad E, Khawaja A, Mak JC, Rogers DF (1996) On muscarinic control of neurogenic mucus secretion in ferret trachea. J Physiol 494:577–586. doi:10.1113/jphysiol.1996.sp021515
Rodrigo GJ, Castro-Rodríguez JA (2015) What is the role of tiotropium in asthma?: a systematic review with meta-analysis. Chest 147:388–396. doi:10.1378/chest.14-1698
Rogers D (2001) Motor control of airway goblet cells and glands. Respir Physiol 125:129–144. doi:10.1016/S0034-5687(00)00209-7
Santus P, Buccellati C, Centanni S, Fumagalli F, Busatto P, Blasi F et al (2012) Bronchodilators modulate inflammation in chronic obstructive pulmonary disease subjects. Pharmacol Res 66:343–348. doi:10.1016/j.phrs.2012.05.007
Scherr A, Schafroth Török S, Jochmann A, Miedinger D, Maier S, Taegtmeyer AB et al (2012) Response to add-on inhaled corticosteroids in COPD based on airway hyperresponsiveness to mannitol. Chest 142:919–926. doi:10.1378/chest.11-2535
Segreti A, Calzetta L, Rogliani P, Cazzola M (2014) Umeclidinium for the treatment of chronic obstructive pulmonary disease. Expert Rev Respir Med 8:665–671. doi:10.1586/17476348.2014.962519
Singh D, Leaker A, Tutuncu A (2011) Efficacy and safety of nebulized glycopyrrolate (EP-101) for administration using high efficiency nebulizer in patients with COPD (Abstract). Eur Respir J 38(Suppl 55):147s
Steinfeld T, Pulido-Rios MT, Chin K, Lee TW, Jasper J, Thomas R et al (2009) In vitro characterization of TD-4208, a lung-selective and long-acting muscarinic antagonist bronchodilator (abstract). Am J Respir Crit Care Med 179:A4553
Sykes DA, Dowling MR, Leighton-Davies J, Kent TC, Fawcett L, Renard E et al (2012) The influence of receptor kinetics on the onset and duration of action and the therapeutic index of NVA237 and tiotropium. J Pharmacol Exp Ther 343:520–528. doi:10.1124/jpet.112.194456
Tashkin DP, Celli B, Senn S, Burkhart D, Kesten S, Menjoge S et al (2008) A 4-year trial of tiotropium in chronic obstructive pulmonary disease. N Engl J Med 359:1543–1554. doi:10.1056/NEJMoa0805800
Taylor RG, Pavia D, Agnew JE, Lopez-Vidriero MT, Newman SP, Lennard-Jones T et al (1986) Effect of four weeks’ high dose ipratropium bromide treatment on lung mucociliary clearance. Thorax 41:295–300
Um SW, Yoo CG, Kim YW, Han SK, Shim YS (2007) The combination of tiotropium and budesonide in the treatment of chronic obstructive pulmonary disease. J Korean Med Sci 22:839–845. doi:10.3346/jkms.2007.22.5.839
Vacca G, Randerath WJ, Gillissen A (2011) Inhibition of granulocyte migration by tiotropium bromide. Respir Res 12:24
van Noord JA, Bantje TA, Eland ME, Korducki L, Cornelissen PJ (2000) A randomised controlled comparison of tiotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. Thorax 55:289–294. doi:10.1136/thorax.55.4.289
van Wyk M, Sommers DK, Snyman JR (1994) Effects of glycopyrrolate on capsaicin-induced cough in normal volunteers treated with captopril. Eur J Clin Pharmacol 46:437–439
Vauquelin G, Charlton SJ (2010) Long-lasting target binding and rebinding as mechanisms to prolong in vivo drug action. Br J Pharmacol 161:488–508. doi:10.1111/j.1476-5381.2010.00936.x
Vehring R, Lechuga-Ballesteros D, Joshi V, Noga B, Dwivedi SK (2012) Cosuspensions of microcrystals and engineered microparticles for uniform and efficient delivery of respiratory therapeutics from pressurized metered dose inhalers. Langmuir 28:15015–15023. doi:10.1021/la302281n
Vézina K, Chauhan BF, Ducharme FM (2014) Inhaled anticholinergics and short-acting beta2-agonists versus short-acting beta2-agonists alone for children with acute asthma in hospital. Cochrane Database Syst Rev 7:CD010283. doi:10.1002/14651858.CD010283.pub2
Wanner A (1986) Effect of ipratropium bromide on airway mucociliary function. Am J Med 81:23–27
Westby M, Benson M, Gibson P (2004) Anticholinergic agents for chronic asthma in adults. Cochrane Database Syst Rev 3:CD003269. doi:10.1002/14651858.CD003269.pub2
Wise RA, Anzueto A, Cotton D, Dahl R, Devins T, Disse B et al (2013) Tiotropium Respimat inhaler and the risk of death in COPD. N Engl J Med 369:1491–1501. doi:10.1056/NEJMoa1303342
ZuWallack R, Allen L, Hernandez G, Ting N, Abrahams R (2014) Efficacy and safety of combining olodaterol Respimat® and tiotropium HandiHaler® in patients with COPD: results of two randomized, double-blind, active-controlled studies. Int J Chron Obstruct Pulmon Dis 9:1133–1144. doi:10.2147/COPD.S72482
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Matera, M.G., Cazzola, M. (2016). Muscarinic Receptor Antagonists. In: Page, C., Barnes, P. (eds) Pharmacology and Therapeutics of Asthma and COPD. Handbook of Experimental Pharmacology, vol 237. Springer, Cham. https://doi.org/10.1007/164_2016_68
Download citation
DOI: https://doi.org/10.1007/164_2016_68
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-52173-2
Online ISBN: 978-3-319-52175-6
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)