BACKGROUND: Nondepolarizing neuromuscular blocking agents (NMBAs) are 
extensively used in the practice of anesthesia and intensive care medicine. 
Their primary site of action is at the postsynaptic nicotinic acetylcholine 
receptor (nAChR) in the neuromuscular junction, but their action on neuronal 
nAChRs have not been fully evaluated. Furthermore, observed adverse effects of 
nondepolarizing NMBAs might originate from an interaction with neuronal nAChRs. 
The aim of this study was to examine the effect of clinically used 
nondepolarizing NMBAs on muscle and neuronal nAChR subtypes.
METHODS: Xenopus laevis oocytes were injected with messenger RNA encoding for 
the subunits included in the human alpha1beta1epsilondelta, alpha3beta2, 
alpha3beta4, alpha4beta2, and alpha7 nAChR subtypes. The interactions between 
each of these nAChR subtypes and atracurium, cisatracurium, d-tubocurarine, 
mivacurium, pancuronium, rocuronium, and vecuronium were studied using an 
eight-channel two-electrode voltage clamp setup. Responses were measured as peak 
current and net charge.
RESULTS: All nondepolarizing NMBAs inhibited both muscle and neuronal nAChRs. 
The neuronal nAChRs were reversibly and concentration-dependently inhibited in 
the low micromolar range. The mechanism (i.e., competitive vs. noncompetitive) 
of the block at the neuronal nAChRs was dependent both on subtype and the NMBA 
tested. The authors did not observe activation of the nAChR subtypes by any of 
the NMBAs tested.
CONCLUSIONS: The authors conclude that nondepolarizing NMBAs 
concentration-dependently inhibit human neuronal nAChRs. The inhibition of the 
presynaptic alpha3beta2 nAChR subtype expressed at the motor nerve ending 
provides a possible molecular explanation for the tetanic and train-of-four fade 
seen during a nondepolarizing neuromuscular block.