1. Allosteric interaction of the neuromuscular blockers vecuronium and pancuronium with recombinant human muscarinic M2 receptors.
- Author
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Cembala TM, Forde SC, Appadu BL, and Lambert DG
- Subjects
- Allosteric Regulation drug effects, Animals, Atropine pharmacology, Binding, Competitive drug effects, CHO Cells, Cricetinae, Cricetulus, Gallamine Triethiodide pharmacology, Humans, Kinetics, Muscarinic Antagonists pharmacology, N-Methylscopolamine metabolism, Pancuronium metabolism, Radioligand Assay, Receptor, Muscarinic M2 antagonists & inhibitors, Receptor, Muscarinic M2 genetics, Recombinant Proteins metabolism, Tritium, Neuromuscular Blocking Agents pharmacology, Pancuronium pharmacology, Receptor, Muscarinic M2 metabolism, Vecuronium Bromide pharmacology
- Abstract
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.
- Published
- 2007
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