Pharmacology of long-acting beta-agonists

When first developed more than 30 years ago, beta-agonists (eg, isoproterenol) did not discriminate between beta 1- and beta 2-subtypes of the beta-adrenoceptor, resulting in effective bronchodilation but also unwanted extrapulmonary side effects. Albuterol later became the prototype selective beta 2-agonist--well tolerated and highly effective in controlling bronchospasm. The major drawback of these more selective beta 2-agonists, however, was their short duration of action (four to six hours). This problem has been largely overcome with the development of a new generation of long-acting beta 2-agonists represented by salmeterol and formoterol (not currently available in the US). This paper summarizes the mechanism of action, potency and receptor selectivity, onset and duration of action, and bronchodilator and nonbronchodilator activity of these long-acting beta 2-agonists.

Preclinical studies have shown both salmeterol and formoterol to be potent and selective at beta 2-adrenoceptors but to have different mechanisms and durations of action. The pharmacologic profiles of these drugs result from prolonged activation of beta 2-adrenoceptors, leading to long-lasting bronchodilation (with no evidence of tolerance or tachyphylaxis) and additional nonbronchodilator properties. The long-acting beta 2-agonists represent a therapeutic advance in the management of asthma.