Past, present and future -: β2-adrenoceptor agonists in asthma management

The beta-adrenoceptor agonists (beta-agonists) have been used to relieve bronchoconstriction for at least 5000 years. beta-agonists are based on adrenaline and early forms, such as isoprenaline, tacked bronchial selectivity and had unpleasant side effects. Modern beta-agonists are more selective for the beta(2)-adrenoceptors (beta(2)-receptors) located in bronchial smooth muscle and have less cardiotoxicity. Traditional beta(2)-adrenoceptor agonists (beta(2)-agonists), such as salbutamol, terbutaline and fenoterol, were characterised by a rapid onset but relatively short duration of action. White valuable as reliever medication, their short duration gave inadequate night-time relief and limited protection from exercise-induced bronchoconstriction. beta(2)-agonists with longer durations of action, formoterot and salmeterol, were subsequently discovered or developed. When combined with inhaled corticosteroids they improved lung function, and reduced symptoms and exacerbations more than an increased dose of corticosteroids. However, tolerance to the bronchprotective effects of long-acting beta(2)-agonists and cross-tolerance to the bronchodilator effects of short-acting beta(2)-agonists is apparent despite use of inhaled corticosteroids. The rote of beta(2)-receptor polymorphisms in the development of tolerance has yet to be fully determined. Formoterol is unique in having both a long-lasting bronchodilator effect (> 12 h) and a fast onset of action (1-3 min from inhalation), making it effective both as maintenance and reliever medication. The recent change in classification from short- and long-acting beta(2)-agonists to rapid-acting and/or long-acting agents reflects the ongoing evolution of beta(2)-agonist therapy. (C) 2004 Elsevier Ltd. All rights reserved.