Antifibrillatory actions of cisatracurium: an atrial specific M2 receptor antagonist.

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Patterson E, Scherlag BJ, Zhou J, Jackman WM, Lazzara R, Coscia D, Po S

Antifibrillatory actions of cisatracurium: an atrial specific M2 receptor antagonist.

J Cardiovasc Electrophysiol. 2008 Aug;19(8):861-8. doi: 10.1111/j.1540-8167.2008.01123.x. Epub 2008 Mar 21.

PubMed ID

18363689 [ View in PubMed

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Abstract

INTRODUCTION: Muscarinic receptor antagonists are proposed to prevent atrial fibrillation (AF), but also facilitate AV conduction, limiting clinical usefulness. METHODS: Cisatracurium, a neuromuscular blocker, was administered to anesthetized dogs (0.05-0.8 mg/kg IV) and was administered to superfused pulmonary vein (PV) tissues in vitro. RESULTS: Dose-dependent suppression of AF induced by premature atrial stimuli was observed under control conditions (n = 3), right vagus nerve stimulation (n = 7), and anterior right ganglionated plexus stimulation (n = 3). AF was prevented (P < 0.0001) concurrent with suppression of the decreased atrial MAP duration/ERP accompanying vagus nerve stimulation without altering AH intervals or sinus cycle length. Although atropine (0.001-0.016 mg/kg, n = 4) suppressed AF (P < 0.04) in association with suppression of atrial MAP shortening induced by vagus nerve stimulation, atropine also prevented sinus cycle length and AH interval prolongation with vagus nerve stimulation, and decreased AV effective and functional refractory periods. In vitro, both cisatracurium and atropine prevented (1) action potential shortening produced by acetylcholine administration and (2) action potential shortening and arrhythmia triggering within PV sleeves produced by local autonomic nerve stimulation, atropine producing competitive inhibition, and cisatracurium producing noncompetitive M(2) muscarinic receptor blockade. CONCLUSIONS: Cisatracurium demonstrates a dose-dependent (1) suppression of AF and atrial action potential shortening accompanying vagus nerve stimulation without facilitating sinus or atrioventricular nodal function and (2) noncompetitive blockade of action potential shortening and triggered firing induced in isolated PVs by local autonomic nerve stimulation. The data are consistent with allosteric binding of cisatracurium to the M(2) muscarinic receptor in canine atrium.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Cisatracurium	Muscarinic acetylcholine receptor M2	Protein	Humans	Unknown	Antagonist	Details