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Physiology of Neuromuscular Transmission and Applied Pharmacology of Muscle Relaxants

  • Neuromuscular Blockade (CA Lien, Section Editor)
  • Published:
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Abstract

Purpose of Review

The purpose of this clinical review is to summarize the physiology of the neuromuscular junction (NMJ) in the normal and denervated state, discuss the pharmacology of the neuromuscular relaxants (NMRs) within and outside the NMJ, and review recent advances in the development of new NMRs and their reversal agents.

Recent Findings

Recent studies have delineated the mechanisms of the non-NMJ, anti-inflammatory effects of non-depolarizing NMRs, mediated by the α7 acetylcholine receptors expressed in innate immune cells (e.g., macrophages). Several chlorofumarate molecules (including gantacurium) have been developed as experimental NMRs, with specific reversal by l-cysteine. Additionally, reversal of existing NMRs (both aminosteroids and benzylisoquinolones) by calabadion 1 and 2 is under investigation.

Summary

New NMRs and reversal agents hold promise for the use in anesthesiology and critical care, with improved pharmacokinetic parameters and more favorable side-effect profiles compared with existing agents. Further research is warranted to exploit the systemic anti-inflammatory properties exhibited by NMRs for other disease processes aside from acute respiratory distress syndrome (ARDS).

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Data Availability

No data sets were directly used in the present manuscript. The content of the manuscript is derived from the publications therein.

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Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

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Funding

Supported in part by grants from the R01GM142042 and Shriners Hospitals Research Philanthropy (to J.A.J.M.)

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Authors and Affiliations

  1. Massachusetts General Hospital, 55 Fruit St. GRJ 404, Boston, MA, USA

    Jamie L. Sparling & J. A. Jeevendra Martyn

  2. Harvard Medical School, Boston, MA, USA

    Jamie L. Sparling & J. A. Jeevendra Martyn

  3. Shriners Hospital for Children, Boston, MA, USA

    J. A. Jeevendra Martyn

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Contributions

J.L.S. prepared the main manuscript text. J.A.J.M. revised the text critically for important intellectual content and prepared Figs. 1A and 1B. Both authors reviewed the manuscript in its entirety and approved the version to be published.

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Correspondence to Jamie L. Sparling.

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All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).

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Sparling, J.L., Martyn, J.A.J. Physiology of Neuromuscular Transmission and Applied Pharmacology of Muscle Relaxants. Curr Anesthesiol Rep 13, 269–278 (2023). https://doi.org/10.1007/s40140-023-00584-y

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