Salmeterol (Astmerole, GR-33343X, SN408D) is a long-acting beta2-adrenergic receptor agonist with Ki value of 1.5 nM for WT β2AR and shows very high selectivity for the WT β2AR(β1Ki/β2Ki ratio of approximately 1500).
Salmeterol is highly lipophilic and diffuses through the lipid bilayer in muscle cell membranes to reach the β2-ARs, explaining its slow onset and long duration of action[2]. Salmeterol has been found to cause a dose-dependent increase in cAMP levels in neutrophils, an effect that is expected to reduce neutrophil-endothelial cell adhesion through inhibition of neutrophil Mac-1 cell surface expression[3].
Salmeterol decreases the production of pro-inflammatory cytokines in a model of allergen-challenged mice that expressed tumor-necrosis factor-alpha, interleukin-1 and interleukin-6[2]. Salmeterol inhibits lipopolysaccharide-induced neutrophil recruitment to the lungs by a mechanism that possibly in part is mediated by an effect on neutrophil CD11b[3].
[1] Isogaya M, et al. Mol Pharmacol. 1998, 54(4):616-22. [2] Zhenli Hu, et al. Cell Mol Immunol. 2012,(3): 267-275. [3] Maris NA, et al. Am J Physiol Lung Cell Mol Physiol. 2004, 286(6):L1122-8.