Structure–Activity Relationship Studies Leading to the Discovery of Highly Water-Soluble and Biocompatible Acyclic Cucurbit[n]uril FY-3451 as a Universal Antagonist That Rapidly Reverses Neuromuscular Blocking Agents In Vivo

Article

Author: Feng, Ke ; Li, Zhan-Ting ; Qi, Qiao-Yan ; Tian, Jia ; Zong, Yang ; Wu, Yan ; Zhang, Jiangshan ; Li, Qian ; Zhang, Dan-Wei ; Liu, Yue-Yang ; Zhou, Wei ; Ma, Da ; Zhuang, Sheng-Yi ; Yu, Shang-Bo ; Lei, Zhuo ; Lin, Furong ; Yang, Jingyu

The development of a reversal agent that can rapidly reverse clinically used nondepolarizing neuromuscular blocking agents (NMBAs) has long been a challenge. Here, we report the synthesis of a series of highly water-soluble acyclic cucurbit[n]urils (acCBs). Systematic structure-activity relationship studies reveal that introducing two propylidene units on the peripheral benzene rings not only remarkably improves the activity of the corresponding derivative acCB6 (FY 3451) in reversing the neuromuscular block of rocuronium, cisatracurium, vecuronium, and pancuronium, the four clinically used NMBAs, through stable inclusion, but also allows for high water-solubility as well as a maximum tolerated dose (2000 mg/kg on rats). In vivo experiments with rats show that, at the identical dose of 25 mg/kg, for rocuronium, vecuronium, and pancuronium, acCB6 can achieve a recovery time shorter than that of sugammadex for rocuronium and, at the dose of 100 mg/kg, realize comparably rapid reversal for cisatracurium.

01 May 2024·European Journal of Anaesthesiology

Extravascular injection of neuromuscular blocking drugs

Review

Author: Van Herreweghe, Imré ; Soetens, Filiep ; Nietvelt, Frederik ; Godschalx, Vincent

Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.

01 Mar 2024·British Journal of Anaesthesia

Under-dosing and over-dosing of neuromuscular blocking drugs and reversal agents: beware of the risks

Author: Blobner, Manfred ; Hunter, Jennifer M

The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.

100 Deals associated with Pancuronium Bromide

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KEGG	Wiki	ATC	Drug Bank
D00492	Pancuronium Bromide	M03AC01	DBSALT000368

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


Pubmed \| Acta Anaesthesiol Scand	Not Applicable	Postoperative Complications \| Neuromuscular Diseases	691	Pancuronium	yepkfjcrxa(kkeowzqhow) = vatmqckuky ljeglrdebx (jqghvotneh ) View more	Positive	01 Oct 1997
				Atracurium/Vecuronium	yepkfjcrxa(kkeowzqhow) = ydnsvnhlzu ljeglrdebx (jqghvotneh ) View more

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