Department of Anesthesiology

You are here

Gantacurium and CW002 do not potentiate muscarinic receptor-mediated airway smooth muscle constriction in guinea pigs.

TitleGantacurium and CW002 do not potentiate muscarinic receptor-mediated airway smooth muscle constriction in guinea pigs.
Publication TypeJournal Article
Year of Publication2010
AuthorsSunaga H, Zhang Y, Savarese JJ, Emala CW
JournalAnesthesiology
Volume112
Issue4
Pagination892-9
Date Published2010 Apr
ISSN1528-1175
KeywordsAcetylcholine, Anesthesia, Animals, Atracurium, Dose-Response Relationship, Drug, Drug Interactions, Guinea Pigs, Heart Rate, Isoquinolines, Lung, Male, Muscle Contraction, Muscle, Smooth, Neuromuscular Depolarizing Agents, Receptor, Muscarinic M2, Receptor, Muscarinic M3, Receptors, Muscarinic, Respiratory System, Vagus Nerve, Vecuronium Bromide
Abstract

BACKGROUND: Neuromuscular blocking agents are an integral component of general anesthesia. In addition to their intended pharmacologic target on skeletal muscle nicotinic receptors, undesirable airway effects (i.e., bronchoconstriction) can result from neuromuscular blocking agents' affinity for airway muscarinic receptors. We questioned whether two new members of a bisquaternary nondepolarizing muscle relaxant family, gantacurium and CW002, demonstrated detrimental effects of airway muscarinic receptors using an in vivo model in guinea pig airways.

METHODS: Urethane-anesthetized male guinea pigs were ventilated through a tracheostomy with continuous digital recordings of pulmonary inflation pressure and heart rate. The dose for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium was defined in the guinea pig. Transient and reproducible changes in pulmonary inflation pressure and heart rate were recorded after vagal nerve stimulation or intravenous injection of acetylcholine before and after pretreatment with cumulatively increasing concentrations of gantacurium, CW002, cisatracurium or a single concentration of rapacuronium.

RESULTS: The doses for 95% twitch suppression for gantacurium, CW002, cisatracurium, and rapacuronium were 0.064 +/- 0.006, 0.012 +/- 0.0006, 0.10 +/- 0.003, and 0.31 +/- 0.05 mg/kg, respectively. Gantacurium, CW002, and cisatracurium were without effects on baseline pulmonary inflation pressures and were devoid of significant interactions with M2 and M3 muscarinic receptors in vivo.

CONCLUSION: These findings suggest that gantacurium and CW002 are devoid of significant effects at airway muscarinic receptors particularly M3 receptors on bronchial smooth musculature at doses several fold higher than those required for functional muscle paralysis.

DOI10.1097/ALN.0b013e3181d32016
Alternate JournalAnesthesiology
PubMed ID20216393
PubMed Central IDPMC2854830
Grant ListGM065281 / GM / NIGMS NIH HHS / United States
R01 GM065281-04 / GM / NIGMS NIH HHS / United States
R01 GM065281-05A1 / GM / NIGMS NIH HHS / United States
R01 GM065281-06 / GM / NIGMS NIH HHS / United States
R01 GM065281-07 / GM / NIGMS NIH HHS / United States