Sympathomimetic bronchodilators: increased selectivity with lung-specific prodrugs

The development of selective bronchodilator β-adrenoceptor agonists is reviewed with emphasis on a pharmacodynamic approach, which is directed to drugs with high specificity for the β2-adrenoceptor, and on a pharmacokinetic approach in which known β2-adrenoceptor agonists are converted to prodrugs with selectivity for the lung. The pharmacodynamic approach has produced drugs that display high specificity for the β2-adrenoceptor but still suffer from side-effects including tremor and palpitations. This is due to the fact that the β2-adrenoceptors present in skeletal muscle and blood vessel are indistinguishable from those in the airways. On the other hand, the prodrug pharmacokinetic approach offers a promising way to obtain selectively acting bronchodilators with significantly fewer side-effects.