Allergology International (Jan 2005)
Clinical Use of β2-adrenergic Receptor Agonists Based on Their Intrinsic Efficacy
Abstract
Clinical choice of β2-adrenergic receptor agonists (β2-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 β2-agonists. Since intrinsic efficacy refers to the ability to activate β2-adrenergic receptors independent of agonist concentration, β2-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 β2-agonists as a reliever medication. In this review, the causal relationship between intrinsic efficacy and desensitization to β2-agonists is examined in tracheal smooth muscle using isometric tension records. Reasonable clinical use of these agonists based on these observations is discussed. When β2-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 β2-agonists (procaterol, salbutamol) was examined after continuous exposure to long-acting β2-agonists (formoterol, salmeterol, tulobuterol). β2- adrenergic desensitization induced by these long-acting β2-agonists was enhanced in proportion to their intrinsic efficacies. On the other hand, under the conditions of impairment of β2-adrenergic receptors, reduced responsiveness to these short-acting β2-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.
Keywords
