Abstract
Chronic obstructive pulmonary disease (COPD) is an increasing global health problem and cause of death. COPD is a chronic inflammatory disease predominantly affecting small airways and lung parenchyma that leads to progressive airway obstruction. However, current therapies fail to prevent either disease progression or mortality. The mainstay of current drug therapy is long-acting bronchodilators. Several once daily inhaled β2-agonists and muscarinic antagonists (and combinations) are now in development. No treatments effectively suppress chronic inflammation in COPD lungs. With better understanding of the inflammatory and destructive process in the pathophysiology of COPD, several new therapeutic targets have been identified. Several mediator antagonists or inhibitors tested in COPD have so far been disappointing, but CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment are more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of the proinflammatory enzymes phosphodiesterase-4, p38 mitogen-activated protein kinase, Janus kinases, NF-κB kinase and PI3 kinase-γ and -δ, but side effects after oral administration are a major limitation so that in future inhaled delivery may be necessary. A new promising approach is reversal of corticosteroid resistance through increasing histone deacetylase-2 (HDAC2) activity. This might be achieved by existing treatments such as theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase-δ inhibitors. Thus although there have been major advances in the development of long-acting bronchodilators for COPD, it has proved difficult to find anti-inflammatory treatments that are safe and effective.
Keywords: Anti-inflammatory, bronchodilator, chemokine, cytokine, histone deacetylase, Janus kinase, nuclear factor-κB, p38 mitogen-activated protein kinase, phosphodiesterase-4, phosphoinositide-3-kinase
Current Medicinal Chemistry
Title:Development of New Drugs for COPD
Volume: 20 Issue: 12
Author(s): Peter J. Barnes
Affiliation:
Keywords: Anti-inflammatory, bronchodilator, chemokine, cytokine, histone deacetylase, Janus kinase, nuclear factor-κB, p38 mitogen-activated protein kinase, phosphodiesterase-4, phosphoinositide-3-kinase
Abstract: Chronic obstructive pulmonary disease (COPD) is an increasing global health problem and cause of death. COPD is a chronic inflammatory disease predominantly affecting small airways and lung parenchyma that leads to progressive airway obstruction. However, current therapies fail to prevent either disease progression or mortality. The mainstay of current drug therapy is long-acting bronchodilators. Several once daily inhaled β2-agonists and muscarinic antagonists (and combinations) are now in development. No treatments effectively suppress chronic inflammation in COPD lungs. With better understanding of the inflammatory and destructive process in the pathophysiology of COPD, several new therapeutic targets have been identified. Several mediator antagonists or inhibitors tested in COPD have so far been disappointing, but CXCR2 antagonists that block pulmonary neutrophil and monocyte recruitment are more promising. Broad spectrum anti-inflammatory drugs may be more effective, and include inhibitors of the proinflammatory enzymes phosphodiesterase-4, p38 mitogen-activated protein kinase, Janus kinases, NF-κB kinase and PI3 kinase-γ and -δ, but side effects after oral administration are a major limitation so that in future inhaled delivery may be necessary. A new promising approach is reversal of corticosteroid resistance through increasing histone deacetylase-2 (HDAC2) activity. This might be achieved by existing treatments such as theophylline, nortriptyline and macrolides, or more selectively by PI3 kinase-δ inhibitors. Thus although there have been major advances in the development of long-acting bronchodilators for COPD, it has proved difficult to find anti-inflammatory treatments that are safe and effective.
Export Options
About this article
Cite this article as:
J. Barnes Peter, Development of New Drugs for COPD, Current Medicinal Chemistry 2013; 20 (12) . https://dx.doi.org/10.2174/0929867311320120005
DOI https://dx.doi.org/10.2174/0929867311320120005 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Treatments for Obesity-Related Hypertension
Current Hypertension Reviews High-Throughput Functional Genomic Methods to Analyze the Effects of Dietary Lipids
Current Pharmaceutical Biotechnology The Pivotal Role of Nitric Oxide: Effects on the Nervous and Immune Systems
Current Pharmaceutical Design Blood Pressure Variability/Dipper/Non-dipper in Hypertension and Diabetes
Current Hypertension Reviews Development of Tissue Engineered Vascular Grafts
Current Pharmaceutical Biotechnology Can't Always Get What you Want? Try an Indirect Route you Just Might Get What you Need: A Study on Access to Genetic Data by Canadian Life Insurers
Current Pharmacogenomics and Personalized Medicine Modifier Gene Studies to Identify New Therapeutic Targets in Cystic Fibrosis
Current Pharmaceutical Design Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)
Current Neuropharmacology G-Protein Coupled Receptors (GPCRs): A Comprehensive Computational Perspective
Combinatorial Chemistry & High Throughput Screening Critical Questions for Preclinical Trials on Safety and Efficacy of Vascular Endothelial Growth Factor-Based Therapeutic Angiogenesis for Ischemic Stroke
CNS & Neurological Disorders - Drug Targets Radiopharmaceuticals Regulations: Current Scenario and the Way Forward
Applied Clinical Research, Clinical Trials and Regulatory Affairs Effects of ACE Inhibitors on Skeletal Muscle
Current Pharmaceutical Design Syntheses and Antitumor Properties of Furoxan Derivatives
Current Organic Chemistry Five Markers Capable to Identify Passive Smoking Exposure Associated with Endothelial Dysfunction in Healthy Individuals
Current Hypertension Reviews Current Algorithms for the Diagnosis of wide QRS Complex Tachycardias
Current Cardiology Reviews Effects of Altered Plasminogen Activator Inhibitor-1 Expression on Cardiovascular Disease
Current Drug Targets Investigating Physical, Psychological and Social Well-being of Older Persons in Jordan
Current Aging Science Role of Vascular Progenitor Cells in Cardiovascular Disease
Current Pharmaceutical Design Inflammation, Endothelial Dysfunction and Arterial Stiffness as Therapeutic Targets in Cardiovascular Medicine
Current Pharmaceutical Design Mood Stabilizers, Oxidative Stress and Antioxidative Defense in Euthymia of Bipolar Disorder
CNS & Neurological Disorders - Drug Targets