Adrenergic agonists that are selective for the β subtype cause bronchial dilation and might be expected to relieve the bronchospasm of an asthmatic attack. Nonselective β-agonists have stimulatory cardiac effects and therefore have limited use in cardiac patients with asthma.
Administration of higher doses of short-acting β-agonists increases duration of action but also increases side effects such as cardiac effects. One approach to avoid these side effects is to use structurally different features that may minimize absorption into systemic circulation. For example, one could use drugs that transform into inactive metabolites upon entry into systemic circulation.
Substituents on the pharmacophore influence whether an analog will be direct- or indirect-acting or a mixture of both. It also influences the specificity for the β-receptor subtypes. Direct-acting analog binds the β-adrenergic receptors directly and generates sympathetic response. Indirect-acting analog causes agonistic effect but without a direct binding to the β-adrenergic receptor, for example, by promoting release of norepinephrine (NE) from the presynaptic terminal or by inhibiting reuptake of released NE.