Selective muscarinic receptor antagonists for airway diseases

Airway tone and airway hyperreactivity are mediated by the parasympathetic nerves that release acetylcholine onto muscarinic receptors (M₁-M₅). Stimulation of M₁ and M₃ muscarinic receptors causes bronchoconstriction. The M₁ muscarinic receptor is excitatory, and facilitates neuronal transmission at the parasympathetic ganglion. The M₂ receptor is an inhibitory prejunctional autoreceptor. The discovery of discrete muscarinic receptor subtypes prompted development of selective muscarinic receptor antagonists. Selective M₃ receptor antagonists and antagonists selective for M₁ and M₃ receptors have recently entered clinical trials and offer much promise for the treatment of airways diseases.