INTERACTION OF NONDEPOLARIZING MUSCLE-RELAXANTS WITH M(2) AND M(3) MUSCARINIC RECEPTORS IN GUINEA-PIG LUNG AND HEART

Background: Neuromuscular blocking agents such as gallamine and pancur onium bind to muscarinic cholinergic receptors and alter parasympathet ically mediated airway caliber and heart rate, In the lungs, acetylcho line induces bronchoconstriction via M(3) muscarinic receptors on airw ay smooth muscle, whereas in the heart M(2) muscarinic receptors media te bradycardia. Moreover, release of acetylcholine from parasympatheti c nerves in the lung is decreased by inhibitory M(2) receptors on the nerves, which represent a negative feedback system. Blockade of these receptors potentiates vagally induced bronchoconstriction, which may b e clinically important if the M(3) receptors on airway muscle are not blocked. These experiments were designed to examine the effects of the newer, nondepolarizing muscle relaxants pipecuronium, doxacurium, and mivacurium on pulmonary and cardiac muscarinic receptors. Methods: Gu inea pigs were anesthetized with urethane, paralyzed with succinylchol ine, and their lungs mechanically ventilated, Pulmonary inflation pres sure and heart rate were measured before and after electrical stimulat ion of both vagus net-yes to evaluate prejunctional M(2) muscarinic re ceptor function and after intravenous acetylcholine to evaluate postju nctional M(3) and M(2) receptor function in the presence of increasing concentrations of pancuronium, mivacurium, pipecuronium, and doxacuri um. Results: Pancuronium was an antagonist for M(2) and M(3) muscarini c receptors. Mivacurium was a more potent antagonist of M(3) than M(2) receptors. Pipecuronium was an antagonist of M(2) but not M(3) recept ors, Doxacurium was not an antagonist of either M(2) or M(3) muscarini c receptors. Only pancuronium and pipecuronium potentiated vagally ind uced bronchoconstriction. With pipecuronium, the potentiation occurred at concentrations greater than those used clinically. Conclusions: Al though pipecuronium is an M(2) receptor antagonist with no M(3) recept or antagonist properties, potentiation of reflex-induced bronchoconstr iction is unlikely, because this effect occurred only at doses greater than those used clinically.