Emerging drugs for chronic obstructive pulmonary disease

被引:24
作者
Matera, Maria Gabriella [2 ]
Calzetta, Luigino [1 ,3 ]
Segreti, Andrea [1 ]
Cazzola, Mario [1 ,3 ]
机构
[1] Univ Roma Tor Vergata, Unit Resp Clin Pharmacol, Dept Internal Med, I-00133 Rome, Italy
[2] Univ Naples 2, Pharmacol Unit, Dept Expt Med, Naples, Italy
[3] IRCCS, Dept Pulm Rehabil, San Raffaele Pisana Hosp, Rome, Italy
关键词
anti-inflammatory agents; bronchodilators; combined therapy; COPD; protease inhibitors; regeneration therapy; RECEPTORS MEDIATE STIMULATION; LONG-ACTING BETA(2)-AGONISTS; ADENOSINE A(2A) RECEPTOR; PLACEBO-CONTROLLED TRIAL; BITTER TASTE RECEPTORS; NITRIC-OXIDE; GUINEA-PIG; PHOSPHODIESTERASE-4; INHIBITORS; LEUKOTRIENE B-4; NEUTROPHIL RECRUITMENT;
D O I
10.1517/14728214.2012.660917
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction: Chronic obstructive pulmonary disease (COPD) is a major public health problem with increasing morbidity and mortality. It is characterized by airflow obstruction that is usually progressive, not fully reversible and does not change markedly over several months. It is associated with an enhanced inflammatory response in the airways and the lung to noxious particles or gases. Therefore, bronchial relaxation and inflammatory response suppression represent a mechanistic approach to the treatment of COPD. Areas covered: This review article is focused on emerging treatment for COPD that is mainly based on new bronchodilators and anti-inflammatory drugs. We also mention new pharmacologic agents whose mechanisms of action target protease activity at the enzymatic level and the potential regenerative therapy for COPD. Expert opinion: New drugs for the treatment of COPD are greatly needed, but development of novel drugs for COPD has proved to be very difficult. Nevertheless, in these last years, several new potential targets have been identified and novel agents for these new targets, as well for known targets, have been developed. Rational therapy depends on elucidating the cellular and molecular mechanisms that are involved in bronchodilation and inflammation in COPD patients, and the structural changes and aberrant repair mechanisms that characterize the pathophysiology of COPD.
引用
收藏
页码:61 / 82
页数:22
相关论文
共 229 条
[41]   Potentiation of neutrophil cyclooxygenase-2 by adenosine: an early anti-inflammatory signal [J].
Cadieux, JS ;
Leclerc, P ;
St-Onge, M ;
Dussault, AA ;
Laflamme, C ;
Picard, S ;
Ledent, C ;
Borgeat, P ;
Pouliot, M .
JOURNAL OF CELL SCIENCE, 2005, 118 (07) :1437-1447
[42]   Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease [J].
Calverley, Peter M. A. ;
Anderson, Julie A. ;
Celli, Bartolome ;
Ferguson, Gary T. ;
Jenkins, Christine ;
Jones, Paul W. ;
Yates, Julie C. ;
Vestbo, Jorgen ;
Calverley, P. M. A. ;
Anderson, J. A. ;
Celli, B. ;
Ferguson, G. T. ;
Jenkins, C. ;
Jones, P. W. ;
Knobil, K. ;
Yates, J. C. ;
Vestbo, J. ;
Cherniack, R. ;
Similowski, T. ;
Cleland, J. ;
Whitehead, A. ;
Wise, R. ;
McGarvey, L. ;
John, M. .
NEW ENGLAND JOURNAL OF MEDICINE, 2007, 356 (08) :775-789
[43]   Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials [J].
Calverley, Peter M. A. ;
Rabe, Klaus F. ;
Goehring, Udo-Michael ;
Kristiansen, Soren ;
Fabbri, Leonardo M. ;
Martinez, Fernando J. .
LANCET, 2009, 374 (9691) :685-694
[44]   Neural regulation of airway smooth muscle tone [J].
Canning, BJ ;
Fischer, A .
RESPIRATION PHYSIOLOGY, 2001, 125 (1-2) :113-127
[45]   The phosphoinositide 3-kinase pathway [J].
Cantley, LC .
SCIENCE, 2002, 296 (5573) :1655-1657
[46]  
CARSTAIRS JR, 1985, AM REV RESPIR DIS, V132, P541
[47]   A new nitrosyl ruthenium complex nitric oxide donor presents higher efficacy than sodium nitroprusside on relaxation of airway smooth muscle [J].
Castro, Patricia F. S. ;
Pereira, Amanda de C. ;
Rogrigues, Gerson J. ;
Batista, Aline C. ;
da Silva, Roberto S. ;
Bendhack, Lusiane M. ;
Rocha, Matheus L. .
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, 2011, 43 (05) :370-377
[48]   Validation of the anti-inflammatory properties of small molecule IκB kinase (IKK)-2 inhibitors by comparison with adenoviral-mediated delivery of dominant-negative IKK1 and IKK2 in human airways smooth muscle [J].
Catley, Matthew C. ;
Sukkar, Maria B. ;
Chung, K. Fan ;
Jaffee, Bruce ;
Liao, Sha-Mei ;
Coyle, Anthony J. ;
Haddad, El-Bdaoui ;
Barnes, Peter J. ;
Newton, Robert .
MOLECULAR PHARMACOLOGY, 2006, 70 (02) :697-705
[49]   Macrolide and occult infection in asthma [J].
Cazzola, M ;
Matera, MG ;
Blasi, F .
CURRENT OPINION IN PULMONARY MEDICINE, 2004, 10 (01) :7-14
[50]   Inhaled combination therapy with long-acting β2-agonists and corticosteroids in stable COPD [J].
Cazzola, M ;
Dahl, R .
CHEST, 2004, 126 (01) :220-237