首页 | 本学科首页   官方微博 | 高级检索  
检索        


Distinct Pharmacologic Properties of Neuromuscular Blocking Agents on Human Neuronal Nicotinic Acetylcholine Receptors: A Possible Explanation for the Train-of-four Fade
Authors:Jonsson  Malin MD  PhD; Gurley  David MS&#x;; Dabrowski  Michael PhD&#x;; Larsson  Olof PhD ; Johnson  Edwin C PhD#; Eriksson  Lars I MD  PhD&#x;
Institution:Jonsson, Malin M.D., Ph.D.*; Gurley, David M.S.?; Dabrowski, Michael Ph.D.?; Larsson, Olof Ph.D.§; Johnson, Edwin C. Ph.D.#; Eriksson, Lars I. M.D., Ph.D.∥
Abstract: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 alpha]1beta]1varepsilon]delta], alpha]3beta]2, alpha]3beta]4, alpha]4beta]2, and alpha]7 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.

Keywords:
点击此处可从《The Journal of the American Society of Anesthesiologists》浏览原始摘要信息
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号