Clinical Use of .BETA.2-adrenergic Receptor Agonists Based on Their Intrinsic Efficacy

• Kume Hiroaki

  Division of Respiratory Medicine, Department of Medicine, Nagoya University Graduate School of Medicine

Bibliographic Information

Other Title

• 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.<br>

Journal

• Allergology International

  Allergology International 54 (1), 89-97, 2005

  Japanese Society of Allergology

Keywords

• airway smooth muscle
• bronchial asthma
• desensitization
• Gs
• long-acting β₂-agonists
• Rho
• β₂-adrenergic receptors

Details

• CRID: 1390001204631168128
• NII Article ID: 10014468835
• NII Book ID: AA11091750
• DOI: 10.2332/allergolint.54.89
• COI: 1:CAS:528:DC%2BD2MXlsV2qsbs%3D
• ISSN: 14401592
• ISSN: 13238930
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015310108?httpAccept=text/xml
• Web Site: http://api.elsevier.com/content/article/PII:S1323893015310108?httpAccept=text/plain
• Web Site: https://search.jamas.or.jp/link/ui/2006305140
• Text Lang: en
• Data Source:
  • JaLC
  • Crossref
  • CiNii Articles
• Abstract License Flag: Disallowed