Muscarinic pharmacology of the airways

Muscarinic receptors have been identified in the airways in several species, including humans, located on airway smooth muscle, secreting cells and on the nerves. M1 receptors are found in sympathetic ganglia in the guinea-pig and in parasympathetic ganglia in humans. M2 receptors (inhibitory autoreceptors) are found in cholinergic parasympathetic nerve terminals in many species, including humans, whereas the muscarinic receptors found on airway smooth muscle and mucus glands belong to the M3 subtype. It is possible that a defect in neuronal M2 receptor function may explain beta-blocker-induced asthma. M2 antagonists such as methoctramine are promising tools for elucidating the role of muscarinic receptor subtypes in the lung. However, they can potentially increase acetylcholine release. This property is not shown by drugs with a higher selectivity for M1 and M3 receptors which are likely to be useful clinically in the treatment of airway disease.