Distinct pharmacologic properties of neuromuscular blocking agents on human neuronal nicotinic acetylcholine receptors: a possible explanation for the train-of-four fade.

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