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Salmeterol has a distinctly slower onset of action due to a much higher degree of partitioning into the lipid bilayer, as well as its unique orientation within the lipid bilayer, both of which facilitate a slow lateral diffusion of salmeterol through a gap between transmembrane helices 2 & 7 of the beta2 receptor wall to access the beta 2 agonist binding site via the lipid bilayer (Szlenk et al, 2020, 2021)