Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors.
Neuromuscular blocking drugs produce muscle weakness by interaction with nicotinic-acetylcholine receptors. Cardiovascular side effects have been reported. In this study the neuromuscular blocking drug vecuronium and the controls gallamine and pancuronium slowed the rate of atropine induced [(3)H]N-methylscopolamine dissociation from Chinese hamster ovary cells expressing recombinant human muscarinic M2 receptors K(off) values min(-1); vecuronium (125 nM), atropine 0.45+/-0.07+blocker 0.04+/-0.02; gallamine (21 nM), atropine 0.42+/-0.05+blocker 0.15+/-0.04; pancuronium(21 nM), atropine 0.36+/-0.03+blocker 0.03+/-0.01). These data indicate that vecuronium, gallamine and pancuronium interact with an allosteric site on the muscarinic M2 receptor (located on the heart) and this may explain some of their cardiac side effects.
Cembala
Thor M
TM
Department of Cardiovascular Sciences (Pharmacology and Therapeutics Group), Division of Anaesthesia, Critical Care and Pain Management, University of Leicester, Leicester Royal Infirmary, Leicester, LE1 5WW, UK.
Forde
Steven C O
SC
Appadu
Balraj L
BL
Lambert
David G
DG
D000494:Allosteric Regulation / Q000187:drug effects; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001667:Binding, Competitive / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D005703:Gallamine Triethiodide / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D018727:Muscarinic Antagonists / Q000494:pharmacology; D019832:N-Methylscopolamine / Q000378:metabolism; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D010197:Pancuronium / Q000378:metabolism / Q000494:pharmacology*; D011869:Radioligand Assay; D043585:Receptor, Muscarinic M2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D014316:Tritium; D014673:Vecuronium Bromide / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D009466:Neuromuscular Blocking Agents; D043585:Receptor, Muscarinic M2; D011994:Recombinant Proteins; D014316:Tritium; D001285:Atropine; D014673:Vecuronium Bromide; D010197:Pancuronium; D005703:Gallamine Triethiodide; D019832:N-Methylscopolamine