Neuromuscular relaxants as antagonists for M2 and M3 muscarinic receptors

Background: Neuromuscular relaxants such as pancuronium bind to M-2 and M-3 muscarinic receptors as antagonists. Blockade of muscarinic receptors in atria of the M-2 subtype mediates tachycardia. In the lung, blockade of M-2 receptors on pansympathetic nerves potentiates vagally induced bronchospasm, whereas blockade of M-3 receptors on bronchial smooth muscle inhibits bronchospasm The current study was designed to quantify the affinity of a series of neuromuscular relaxants for the M-2 and M-3 muscarinic receptors, which were individually stably transfected in Chinese hamster ovary cell lines. Methods: Competitive radioligand binding assays determined the relative binding affinities of the neuromuscular relaxants pancuronium, succinylcholine, mivacurium, doxacurium, atracurium, rocuronium, gallamine, and pipecuronium for the muscarinic receptor in the presence of a muscarinic receptor antagonist (H-3-QNB) in membranes prepared from cells individually expressing either the M-2 or M-3 muscarinic receptor. Results: All muscle relaxants evaluated displaced H-3-QNB from muscarinic receptors. The relative order of potency for the M, muscarinic receptor (highest to lowest) was pancuronium, gallamine, rocuronium, atracurium, pipecuronium, doxacurium, mivacurium, and succinylcholine. The relative order of potency for the M-3 muscarinic receptor (highest to lowest) was pancuronium, atracurium, pipecuronium, rocuronium, mivacurium, gallamine, succinylcholine, and doxacurium. Conclusions: All neuromuscular relaxants studied had affinities for the M-2 and M-3 muscarinic receptor, but only pancuronium and gallamine had affinities within the range of concentrations achieved with clinical use. The high affinities of gallamine and pancuronium for the M-2 muscarinic receptor are consistent with a mechanism of M-2 receptor blockade in relaxant-induced tachycardia.