Interaction of nondepolarizing muscle relaxants with M 2 and M 3 muscarinic receptors in guinea pig lung and heart

Olubunmi A. Okanlami, Allison Fryer, Carol Hirshman

Research output: Contribution to journalArticle

29 Scopus citations

Abstract

Background: Neuromuscular blocking agents such as gallamine and pancuronium bind to muscarinic cholinergic receptors and alter parasympathetically mediated airway caliber and heart rate. In the lungs, acetylcholine induces bronchoconstriction via M 3 muscarinic receptors on airway smooth muscle, whereas in the heart M 2 muscarinic receptors mediate bradycardia. Moreover, release of acetylcholine from parasympathetic 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 be 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: Guinea pigs were anesthetized with urethane, paralyzed with succinylcholine, and their lungs mechanically ventilated. Pulmonary inflation pressure and heart rate were measured before and after electrical stimulation of both vagus nerves to evaluate prejunctional M 2 muscarinic receptor function and after intravenous acetylcholine to evaluate postjunctional M 3 and M 2 receptor function in the presence of increasing concentrations of pancuronium, mivacurium, pipecuronium, and doxacurium. Results: Pancuronium was an antagonist for M 2 and M 3 muscarinic 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 receptors. Doxacurium was not an antagonist of either M 2 or M 3 muscarinic receptors. Only pancuroniumand pipecuronium potentiated vagally induced bronchoconstriction. With pipecuronium, the potentiation occurred at concentrations greater than those used clinically. Conclusions: Although pipecuronium is an M 2 receptor antagonist with no M 3 receptor antagonist properties, potentiation of reflex-induced bronchoconstriction is unlikely, because this effect occurred only at doses greater than those used clinically.

Original languageEnglish (US)
Pages (from-to)155-161
Number of pages7
JournalAnesthesiology
Volume84
Issue number1
DOIs
Publication statusPublished - Jan 1996
Externally publishedYes

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Keywords

  • Muscarinic receptors: M ; M
  • Neuromuscular relaxants: doxacurium; mivacurium; pancuronium; pipecuronium

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine

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