Effect of 2-(acetyloxy)-N,N,N-trimethylpropan-1-aminium on Tracheal Smooth Muscle Reactivity

Muscarinic receptor subtypes have been identified on airways of several mammalian species, including humans. M1-receptors are found in airway ganglia, M2-receptors (autoreceptors) are present in cholinergic postganglionic nerves at the prejunctional level, whereas the muscarinic receptor subtypes found in airway smooth muscle are of the M3-receptor subtype (1, 12). Methacholine 2-(acetyloxy)-N,N,N-trimethylpropan1-aminium is primarily used to diagnose bronchial hyperreactivity, which appears in asthma and in chronic obstructive pulmonary disease. This is accomplished through the bronchial challenge test, or methacholine challenge, in which a subject inhales aerosolized methacholine, leading to bronchoconstriction. Methacholine has a charged quaternary amine structure, rendering it insoluble to lipid cell membranes. Methacholine has a β-methyl group which provides selectivity towards M-type receptors as compared to Ntype receptors. The quaternary ammonium group is essential for activity. The ester however makes it susceptible to the enzyme acetylcholine esterase (2). It is highly active at all of the muscarinic receptors, but has little effect on the nicotinic receptors.