Find in Library

Bronchodilators and anti-inflammatory agents are the mainstream treatments in chronic obstructive and pulmonary disease (COPD) and asthma. The combination of β₂ adrenergic receptor (β₂AR) agonists and muscarinic antagonists shows superior bronchoprotective effects compared to these agents individually. Navafenterol (AZD8871) is a single-molecule, dual pharmacology agent combining muscarinic antagonist and β₂AR agonist functions, currently in development as a COPD therapeutic. In precision-cut human lung slices (hPCLS), we investigated the bronchoprotective effect of navafenterol against two non-muscarinic contractile agonists, histamine and thromboxane A₂ (TxA₂) analog (U46619). Navafenterol pre-treatment significantly attenuated histamine-induced bronchoconstriction and β₂AR antagonist propranolol reversed this inhibitory effect. TxA₂ analog-induced bronchoconstriction was attenuated by navafenterol pre-treatment, albeit to a lesser magnitude than that of histamine-induced bronchoconstriction. Propranolol completely reversed the inhibitory effect of navafenterol on TxA₂ analog-induced bronchoconstriction. In the presence of histamine or TxA₂ analog, navafenterol exhibits bronchoprotective effect in human airways and it is primarily mediated by β₂AR agonism of navafenterol.