Membrane-Facilitated Receptor Access and Binding Mechanisms of Long-Acting β2-Adrenergic Receptor Agonists.

ABSTRACT: The drugs salmeterol, formoterol, and salbutamol constitute the frontline treatment of asthma and other chronic pulmonary diseases. These drugs activate the β2-adrenergic receptors (β2-AR), a class A G protein-coupled receptor (GPCR), and differ significantly in their clinical onset and duration of actions. According to the microkinetic model, the long duration of action of salmeterol and formoterol compared with salbutamol were attributed, at least in part, to their high lipophilicity and increased local concentrations in the membrane near the receptor. However, the structural and molecular bases of how the lipophilic drugs reach the binding site of the receptor from the surrounding membrane remain unknown. Using a variety of classic and enhanced molecular dynamics simulatio

SUBMITTER: Szlenk CT 

PROVIDER: S-EPMC8626642 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature