Calabadion: A new agent to reverse the effects of benzylisoquinoline and steroidal neuromuscular-blocking agents.
Ulrike Hoffmann,Martina Grosse-Sundrup,Katharina Eikermann-Haerter,S. Zaremba,Cenk Ayata,Ben Zhang,Da Ma,Lyle Isaacs,Matthias Eikermann +8 more
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TLDR
Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents and did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension.Abstract:
To evaluate whether calabadion 1, an acyclic member of the Cucurbit[n]uril family of molecular containers, reverses benzylisoquinoline and steroidal neuromuscular-blocking agent effects.A total of 60 rats were anesthetized, tracheotomized, and instrumented with IV and arterial catheters. Rocuronium (3.5 mg/kg) or cisatracurium (0.6 mg/kg) was administered and neuromuscular transmission quantified by acceleromyography. Calabadion 1 at 30, 60, and 90 mg/kg (for rocuronium) or 90, 120, and 150 mg/kg (for cisatracurium), or neostigmine/glycopyrrolate at 0.06/0.012 mg/kg were administered at maximum twitch depression, and renal calabadion 1 elimination was determined by using a H NMR assay. The authors also measured heart rate, arterial blood gas parameters, and arterial blood pressure.After the administration of rocuronium, resumption of spontaneous breathing and recovery of train-of-four ratio to 0.9 were accelerated from 12.3 ± 1.1 and 16.2 ± 3.3 min with placebo to 4.6 ± 1.8 min with neostigmine/glycopyrrolate to 15 ± 8 and 84 ± 33 s with calabadion 1 (90 mg/kg), respectively. After the administration of cisatracurium, recovery of breathing and train-of-four ratio of 0.9 were accelerated from 8.7 ± 2.8 and 9.9 ± 1.7 min with placebo to 2.8 ± 0.8 and 7.6 ± 2.1 min with neostigmine/glycopyrrolate to 47 ± 13 and 87 ± 16 s with calabadion 1 (150 mg/kg), respectively. Calabadion 1 did not affect heart rate, mean arterial blood pressure, pH, carbon dioxide pressure, and oxygen tension. More than 90% of the IV administered calabadion 1 appeared in the urine within 1 h.Calabadion 1 is a new drug for rapid and complete reversal of the effects of steroidal and benzylisoquinoline neuromuscular-blocking agents.read more
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Journal ArticleDOI
Stimuli Responsive Systems Constructed Using Cucurbit[n]uril-Type Molecular Containers
TL;DR: It is shown how the free energy associated with the formation of host–guest complexes of CB[n]-type receptors can drive conformational changes of included guests like triazene–arylene foldamers and cationic calix[4]arenes, as well as induced conformations of the hosts themselves.
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Nanomolar Binding of Steroids to Cucurbit[n]urils: Selectivity and Applications
Alexandra I. Lazar,Frank Biedermann,Kamila R. Mustafina,Khaleel I. Assaf,Andreas Hennig,Werner M. Nau +5 more
TL;DR: Fluorescence displacement titrations and isothermal titration calorimetry provided up to nanomolar binding affinities in aqueous solution for these hydrophobic target molecules, exceeding the values of known synthetic receptors.
Journal ArticleDOI
Reversal of residual neuromuscular block: complications associated with perioperative management of muscle relaxation.
TL;DR: Although sugammadex has been shown to rapidly reverse profound neuromuscular block from aminosteroidal agents, there is currently no evidence that sugamsadex is superior to neostigmine in its effect on POPCs.
Journal ArticleDOI
Comparative effectiveness of Calabadion and sugammadex to reverse non-depolarizing neuromuscular blocking agents
Friederike Haerter,Jeroen C. P. Simons,Urs Foerster,Ingrid Moreno Duarte,Daniel Diaz-Gil,Shweta Ganapati,Katharina Eikermann-Haerter,Cenk Ayata,Ben Zhang,Manfred Blobner,Lyle Isaacs,Matthias Eikermann,Matthias Eikermann +12 more
TL;DR: Calabadion 2 reverses NMB induced by benzylisoquinolines and steroidal NMBAs in rats more effectively, i.e., faster than sugammadex, and is eliminated in the urine and well tolerated in rats.
Journal ArticleDOI
In vivo reversal of general anesthesia by cucurbit[7]uril with zebrafish models
Huanxian Chen,Judy Yuet-Wa Chan,Shengke Li,Jessica J. Liu,Ian Wyman,Simon Ming-Yuen Lee,Donal H. Macartney,Ruibing Wang +7 more
TL;DR: The in vitro supramolecular host–guest complexations between macrocyclic cucurbit[7]uril (CB[7]) and a commonly used general anesthetic in fish are demonstrated and the in vivo reversal effect of CB to general anesthesia induced by TM with zebrafish models is reported for the first time.
References
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MonographDOI
Supramolecular Chemistry: Concepts and Perspectives
TL;DR: From molecular to supramolescular chemistry: concepts and language of supramolecular chemistry, molecular recognition, information, complementarity molecular receptors - design principles and more.
Journal ArticleDOI
Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome
Laurent Papazian,Jean-Marie Forel,Arnaud Gacouin,Christine Penot-Ragon,Gilles Perrin,Anderson Loundou,Samir Jaber,Jean-Michel Arnal,Didier Perez,Jean-Marie Seghboyan,Jean-Michel Constantin,Pierre Courant,Jean-Yves Lefrant,Claude Guérin,Gwenaël Prat,Sophie Morange,Antoine Roch +16 more
TL;DR: In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness.
Journal ArticleDOI
Cucurbituril homologues and derivatives: new opportunities in supramolecular chemistry.
TL;DR: This Account is a compilation of recent literature covering the syntheses of the homologues and derivatives, and their supramolecular chemistry of cucurbituril, a synthetic receptor.
Journal ArticleDOI
Functionalized cucurbiturils and their applications.
TL;DR: This tutorial review describes the recent advances and challenges in the functionalization of CBs along with the applications of functionalized CBs.
Journal ArticleDOI
Residual neuromuscular block is a risk factor for postoperative pulmonary complications: A prospective, randomised, and blinded study of postoperative pulmonary complications after atracurium, vecuronium and pancuronium
H. Berg,Jørgen Viby-Mogensen,J. Roed,C. R. Mortensen,J. Engbæk,L. T. Skovgaard,J. J. Krintel +6 more
TL;DR: The aim of this study was to compare the incidence of POPC following the use of pancuronium, atracurium, and vecuronium and to examine the effect of residual neuromuscular block on the incidence.