The Role of Pirenzepine-sensitive (M₁) Muscarinic Receptors in Vagally Mediated Bronchoconstriction in Humans

In a double-blind randomized study, we compared the effects of the M1-selective muscarinic receptor antagonists pirenzepine and the nonselective antagonist ipratropium bromide on bronchoconstriction induced by inhaled sulfur dioxide (SO2) and methacholine in atopic volunteers. Both inhaled pirenzepine (70 µg) and ipratropium bromide (7 µg) significantly inhibited vagally mediated bronchoconstriction by SO2 to the same extent (p < 0.02). However, at this dose, pirenzepine had no effect on methacholine-induced bronchoconstriction, whereas ipratropium bromide gave significant protection (p < 0.02). This indicates that vagaily mediated bronchoconstriction in humans can be inhibited by blockade of pirenzepine-sensitive (M1) muscarinic receptors probably present on a different site from muscarinic receptors at the neuromuscular junction and presumably localized to parasympathetic ganglia. Pirenzepine may be useful in investigating ganglionic function and could be beneficial therapeutically in airway disease.