Advances in adrenergic receptors for the treatment of chronic obstructive pulmonary disease: 2023 update.

INTRODUCTION

Strong scientific evidence and large experience support the use of β-agonists for the symptomatic alleviation of COPD. Therefore, there is considerable effort in discovering highly potent and selective β-agonists.

AREAS COVERED

Recent research on novel β-agonists for the treatment of COPD. A detailed literature search was performed in two major databases (PubMed/MEDLINE and Scopus) up to September 2023."

EXPERT OPINION

Compounds that preferentially activate a G- or β-arrestin-mediated signaling pathway via β- adrenoceptors (ARs) are more innovative. Pepducins, which target the intracellular region of β-AR to modulate receptor signaling output, have the most interesting profile from a pharmacological point of view. They stabilize the conformation of the β-AR and influence its signaling by interacting with the intracellular receptor-G protein interface. New bifunctional drugs called muscarinic antagonist-β agonist (MABA), which have both muscarinic receptor (mAChR) antagonism and β-agonist activity in the same molecule, are a new opportunity. However, all tested compounds have been shown to act predominantly as mAChR antagonists or β-agonists. An intriguing idea is to utilize allosteric modulators that bind to β-ARs at sites different than those bound by orthosteric ligands to augment or reduce the signaling transduced by the orthosteric ligand.