Olodaterol is a novel, long-acting beta2-adrenergic agonist (LABA) that exerts its pharmacological effect by binding and activating beta2-adrenergic receptors located primarily in the lungs.

β2-adrenoceptor:0.1 nM (EC50)

Olodaterol shows a potent, nearly full agonistic response at the hβ2-adrenoceptor (EC50=0.1 nM; intrinsic activity=88% compared with isoprenaline) and a significant selectivity profile (241- and 2299-fold against the hβ1- and hβ3-ARs, respectively). Likewise, olodaterol is able to potently reverse contraction induced by different stimuli in isolated human bronchi[2].

Olodaterol is a long acting β2-agonist that induces bronchodilation up to 24 h after dosing in patients with chronic obstructive pulmonary disease (COPD) . Olodaterol dose-dependently attenuates cell influx and pro-inflammatory mediator release in murine and guinea pig models of pulmonary inflammation. Olodaterol attenuates pro-inflammatory mediator release from human parenchymal explants and whole blood and reduced expression of CD11b adhesion molecules on granulocytes, but without direct effects on IL-8-induced neutrophil transwell migration[3]. Once-daily olodaterol 5 μg is an effective therapy in improving lung function and symptomatic outcomes in patients with moderate to very severe (COPD) receiving other maintenance therapy, with a satisfactory safety profile[4].

To determine the functional potency of the different agonists against the different hβ-ARs, changes in intracellular cAMP levels are determined with CHO cells in suspension and a 384-well plate format. In brief, cells are stimulated with the respective agonists at different concentrations in Hanks' buffered saline solution. Cells are lysed by using Alphascreen reagents. After 2 h, plates are read on an Envision plate reader. The concentration of cAMP in the samples is calculated from a standard curve[2].