Clinical Use of β2-adrenergic Receptor Agonists Based on Their Intrinsic Efficacy

Abstract

Clinical choice of β 2 -adrenergic receptor agonists (β 2 -agonists) is based on the parameter of receptor selectivity, potency, and duration of action. The guidelines for asthma management describe nothing about intrinsic efficacy concerning the use of β 2 -agonists. Since intrinsic efficacy refers to the ability to activate β 2 -adrenergic receptors independent of agonist concentration, β 2 -adrenergic desensitization may be associated with intrinsic efficacy. However, little is currently known whether chronic administration of high intrinsic efficacy drugs interferes with the effects of β 2 -agonists as a reliever medication. In this review, the causal relationship between intrinsic efficacy and desensitization to β 2 -agonists is examined in tracheal smooth muscle using isometric tension records. Reasonable clinical use of these agonists based on these observations is discussed. When β 2 -agonists intrinsic efficacy was measured as relaxation response (the maximum inhibitory effects against 1 μM methacholine-induced contraction), their rank order was : isoproterenol = procaterol = formoterol > salbutamol > salmeterol >> tulobuterol. Next, the subsequent response to short-acting β 2 -agonists (procaterol, salbutamol) was examined after continuous exposure to long-acting β 2 -agonists (formoterol, salmeterol, tulobuterol). β 2 - adrenergic desensitization induced by these long-acting β 2 -agonists was enhanced in proportion to their intrinsic efficacies. On the other hand, under the conditions of impairment of β 2 -adrenergic receptors, reduced responsiveness to these short-acting β 2 -agonists was enhanced in inverse proportion to the intrinsic efficacy. Although the clinical relevance of these results is still unclear, our data may provide evidence that weak partial agonists are useful as a controller medication, whereas full or strong agonists are useful as a reliever medication.