Figure 1

Dual bronchodilation induced by the fixed-dose co-formulation of indacaterol/glycopyrronium. Indacaterol induces a long-lasting relaxation of airway smooth muscle via a prolonged activation of β₂-adrenergic receptors, coupled through a stimulatory G protein (consisting of α_s, β and γ subunits) to adenylyl cyclase, which catalyzes the synthesis of the intracellular second messenger cAMP. The bronchodilation induced by indacaterol is greatly enhanced by glycopyrronium, which provides a prolonged competitive blockade of M₃ muscarinic receptors. Indeed, glycopyrronium dissociates very slowly from these receptors, whereas it quickly detaches from M₂ receptors. Although the latter may partially contribute to bronchoconstriction via inactivation of adenylyl cyclase mediated by an inhibitory G protein (consisting of α_i, β and γ subunits), they are, however, primarily responsible for pre-junctional inhibition of acetylcholine release.