The -adrenoceptor agonists (-agonists) have been used to relieve bronchoconstriction for at least 5000 years. -agonists are based on adrenaline and early forms, such as isoprenaline, lacked bronchial selectivity and had unpleasant side effects. Modern -agonists are more selective for the -adrenoceptors (-receptors) located in bronchial smooth muscle and have less cardiotoxicity. Traditional -adrenoceptor agonists (-agonists), such as salbutamol, terbutaline and fenoterol, were characterised by a rapid onset but relatively short duration of action. While valuable as reliever medication, their short duration gave inadequate night-time relief and limited protection from exercise-induced bronchoconstriction. -agonists with longer durations of action, formoterol 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 -agonists and cross-tolerance to the bronchodilator effects of short-acting -agonists is apparent despite use of inhaled corticosteroids. The role of -receptor polymorphisms in the development of tolerance has yet to be fully determined.
Formoterol is unique in having both a long-lasting bronchodilator effect 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 -agonists to rapid-acting and/or long-acting agents reflects the ongoing evolution of -agonist therapy.