Methacholine chloride 100mg powder for nebuliser solution vials

Asthma is a complicated condition associated with airway remodelling, including the proliferation of airway smooth muscle (ASM) and altered extracellular matrix, aberrant pro-inflammatory immune responses, and excessive ASM contraction leading to decreased lung function.[A229598][A229603] Excessive ASM contraction in response to contractile agonists, a phenomenon termed airway hyperresponsiveness (AHR), is a physical manifestation of the altered pulmonary physiology in asthma.[A229603] Although numerous factors, such as increased ASM levels, pro-contractile molecules, pro-inflammatory cytokines, and growth factors, contribute to AHR, one of the key factors in determining ASM tone is regulated by vagal parasympathetic nerve innervation.[A229598][A229603][A229613] The response to acetylcholine and other cholinergic agonists at these neuromuscular junctions is predominantly controlled by inhibitory G_i-coupled M₂ and excitatory G_q-coupled M₃ muscarinic acetylcholine receptors (mAChRs). Activation of M₃ receptors results in ASM contraction and resulting bronchoconstriction through downstream calcium-dependent signalling pathways, while M₂ activation inhibits neuronal acetylcholine release.[A229603][A229613][A229618]

Methacholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes.[A229623][A229628][A229633] However, in the context of AHR, methacholine's ability to induce bronchoconstriction through M₃ receptors is clinically relevant.[A229603][A229618][A229643] In addition, M₃ agonism may increase the release of pro-inflammatory cytokines, further contributing to AHR.[A17070] The inhibitory effect of M₂ agonism by methacholine is likely also important, as shown by animal studies using mice with impaired M₂ function, and by observations that eosinophilic inflammation, such as occurs in asthma, negatively impacts M₂ function.[A229613] Hence, asthmatic patients are more sensitive to inhaled cholinergic agonists such as methacholine; this forms the basis for the methacholine challenge test, which diagnoses AHR through an increased methacholine-induced response.[A229648][L31763]