(2-하이드록시프로필)트리메틸람모늄아세테이트

V - Various

QV - Various

Methacholine is a non-specific cholinergic agonist (parasympathomimetic) that acts through muscarinic receptors in the lungs to induce bronchoconstriction, which is more significant in patients with asthma than those without. Therefore, methacholine carries a risk of severe bronchoconstriction, especially in patients with pre-existing reduced pulmonary function (typically baseline FEV₁ < 60% or < 1.5 L, at least in adults), clinically apparent asthma or wheezing, or other health conditions such as uncontrolled hypertension, aortic aneurysm, or history of myocardial infarction or stroke. Use in patients with epilepsy, vagotonia, peptic ulcer disease, thyroid disease, urinary tract obstruction or other conditions that could be adversely affected by a cholinergic agent is not recommended. Also, there is a potential risk to healthcare workers administering the methacholine challenge test; proper precautions and protective equipment should be used as needed.

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. 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. 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. 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. Methacholine is a non-specific mAChR agonist, capable of acting on all mAChR subtypes. However, in the context of AHR, methacholine's ability to induce bronchoconstriction through M₃ receptors is clinically relevant. In addition, M₃ agonism may increase the release of pro-inflammatory cytokines, further contributing to AHR. 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. 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.