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• W1967637447 abstract "Background Nondepolarizing neuromuscular blocking agents (NMBAs) are classic competitive-inhibitors at the muscle nicotinic acetylcholine receptor (nAChR). Although the fetal subtype muscle nAChR has been extensively studied at a molecular level, less is known about the interaction between nondepolarizing NMBAs and the human adult muscle nAChR. The aim of this study was to investigate the effect of clinically used nondepolarizing NMBAs at human adult muscle nAChRs and the mechanisms behind the inhibition. Methods Human subunits for the adult alpha(1)beta(1)delta(epsilon) muscle nAChR were cloned and expressed into Xenopus oocytes and thereafter studied with two-electrode voltage clamp. The effect of the clinically used nondepolarizing NMBAs, including atracurium, cis-atracurium, mivacurium, pancuronium, rocuronium, vecuronium, and d-tubocurarine, on acetylcholine-induced and dimethylphenylpiperazinium-induced currents were investigated. Results All nondepolarizing NMBAs tested inhibited acetylcholine- and dimethylphenylpiperazinium-induced currents in human adult alpha(1)beta(1)delta(epsilon) muscle nAChRs, and no receptor activation was seen. Interestingly, acetylcholine desensitized the human adult alpha(1)beta(1)delta(epsilon) muscle type receptor and attenuated the inhibition caused by nondepolarizing NMBAs, as evident by lack of increase in IC(50) values for the nondepolarizing NMBAs with increased concentrations of acetylcholine. In contrast, dimethylphenylpiperazinium-induced currents were competitively inhibited by the nondepolarizing NMBAs. Conclusions This study demonstrates that nondepolarizing NMBAs inhibit human adult muscle nAChRs expressed in Xenopus oocytes by mixed mechanisms. When using the nondesensitizing agonist dimethylphenylpiperazinium, inhibition by the NMBA is competitive, whereas activation with high concentrations of acetylcholine in combination with NMBA induces a noncompetitive inhibition, which the authors speculate can involve receptor desensitization similar to that observed in the neuromuscular junction." @default.
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• W1967637447 date "2009-06-01" @default.
• W1967637447 modified "2023-10-16" @default.
• W1967637447 title "Pharmacological Characteristics of the Inhibition of Nondepolarizing Neuromuscular Blocking Agents at Human Adult Muscle Nicotinic Acetylcholine Receptor" @default.
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• W1967637447 doi "https://doi.org/10.1097/aln.0b013e31819fade3" @default.
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