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


CONCLUSIONS
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.
Sunaga
Hiroshi
H
Department of Anesthesiology, Weill Cornell Medical College, New York, New York, USA.
Zhang
Yi
Y
Savarese
John J
JJ
Emala
Charles W
CW
D000109:Acetylcholine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D001279:Atracurium / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007546:Isoquinolines / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology*; D043585:Receptor, Muscarinic M2 / Q000187:drug effects; D043587:Receptor, Muscarinic M3 / Q000187:drug effects; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012137:Respiratory System / Q000187:drug effects*; D014630:Vagus Nerve / Q000502:physiology; D014673:Vecuronium Bromide / Q000031:analogs & derivatives / Q000494:pharmacology
C542547:CW 002; D007546:Isoquinolines; D009467:Neuromuscular Depolarizing Agents; D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D011976:Receptors, Muscarinic; D001279:Atracurium; D014673:Vecuronium Bromide; C082938:rapacuronium; C451919:gantacurium; D000109:Acetylcholine; C101584:cisatracurium