Current and novel bronchodilators in respiratory disease.
Current Opinion in Pulmonary Medicine.
20(1):73-86, January 2014.
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Purpose of review: [beta]2-Agonists and muscarinic antagonists are widely used to treat asthma and chronic obstructive pulmonary disease (COPD), and a number of novel drug targets are being investigated for potential clinical utility. This review will summarize current developments in the field.
Recent findings: The clinical effectiveness of a number of once a day inhaled [beta]2-agonists and muscarinic antagonists is a major advance providing sustained bronchodilation in asthma and COPD. The identification of novel targets (e.g. bitter taste receptor TASR2), the demonstration of clinical effectiveness of others [e.g. phosphodiesterase (PDE)3/4] and exploring the potential of inverse agonists/biased agonists are evidence of continuing interest in the development of novel bronchodilators.
Summary: Novel long-acting [beta]2-agonists (e.g. indacaterol, vilanterol, olodaterol and carmoterol) and muscarinic antagonists (e.g. tiotropium, aclidinium, glycopyrronium and umeclidinium bromide) document sustained bronchodilation and their combination provides additional benefits over monotherapy. Not surprisingly, inhaled long-acting [beta]2-agonist and long-acting muscarinic antagonists remain the drugs of choice for maintenance bronchodilation. However, there is a continued interest in developing novel bronchodilators illustrated by the clinical effectiveness of long acting mixed PDE3/4 inhibitors, vasointestinal peptide adenylyl cyclase agonists and inverse agonists/biased agonists for the [beta]2-adrenoceptor, and the identification of intracellular (e.g. Rho kinase, exchange proteins activated by cyclic AMP) and cell surface (e.g. TAS2R, natriuretic peptide receptor) targets.
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