Methacholine is a parasympathomimetic bronchoconstrictor used to diagnose bronchial hyperreactivity in subjects who do not have clinically apparent asthma. It can be found under the brand name Provocholine. Asthma is a complex condition associated with phenomena such as airway hyperresponsiveness (AHR), in which the smooth muscle in the airways (ASM) excessively contracts in response to stimuli, reducing pulmonary function and causing symptoms such as difficulty breathing. Although the underlying pathology of AHR is complex, ASM contraction can be stimulated by cholinergic agonists that activate M3 muscarinic receptors that stimulate ASM contraction. Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction. In patients with AHR, a lower dose of methacholine is required to induce bronchoconstriction, which forms the basis for the methacholine challenge test to diagnose AHR. Activation of M3 receptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while M2 activation inhibits neuronal acetylcholine release. Possible side effects of using methacholine may include headache, sore throat, nausea, and dizziness.

Methacholine M3 Bronchoconstriction Pathway References