New Drug Developments for Neuromuscular Blockade and Reversal: Gantacurium, CW002, CW011, and Calabadion

Boer, Hans D. de; Carlos, Ricardo Vieira

doi:10.1007/s40140-018-0262-9

Cited by 14 publications

(5 citation statements)

References 23 publications

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“…However, after reviewing total 50 trials including 4,151 patients, the Cochrane Collaboration concluded that Sch is superior to rocuronium for RSI, as Sch could achieve acceptable intubating conditions faster (by 30-60 s) than rocuronium, thus rocuronium should be used as an alternative only in cases where Sch is contraindicated 82. Recently, another two new NMBAs (gantacurium and CW002) exhibit relatively rapid onset (90 s) and their neuromuscular blocking effect could be effectively reversed by cholinesterase inhibitors and cysteine 83, however they are not clinically approved yet and further studies need to be conducted to confirm their safety in humans 84. Therefore, Sch still plays an irreplaceable role as a NMBA in situations that require RSI and is still clinically used extensively in anesthesia around the globe.…”

Section: Discussionmentioning

confidence: 99%

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent

Zhang

Qian

et al. 2019

Theranostics

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Succinylcholine (Sch) is the only depolarizing neuromuscular blocking agent widely used for rapid sequence induction in emergency rooms. Unfortunately, a variety of (sometimes lethal) adverse effects, such as hyperkalemia and cardiac arrest, are associated with its use, and currently there are no specific antidotes to reverse Sch or to treat these side-effects. Methods: The binding behaviors of Sch and several synthetic receptors, including cucurbit[7]uril, sulfo-calix[4]arene and water-soluble carboxylatopillar[6]arene (WP[6]), were first investigated. With a mouse model, a leathal dose of Sch was selected for evaluation of the antidotal effects of these synthetic receptors on Sch induced mortality. The antidotal effects of a selected synthetic receptor, WP[6], on Sch induced cardiac arrhythmias, hyperkalemia, rhabdomyolysis and paralysis were subsequently evaluated with rat and mouse models. The reversal mechanism was also investigated at a cellular level. Results: All of these macrocyclic molecules exhibited relatively high binding affinities with Sch in vitro . In a Sch-overdosed mouse model, immediate injection of these synthetic receptors right after Sch administration increased the overall survival rate, with WP[6] standing out with the most effective antidotal effects. In addition, administration of WP[6] also reversed the paralysis induced by Sch in a mouse model. Moreover, infusion of WP[6] to Sch-overdosed rats reduced the incidence of cardiac arrhythmia, inhibited the otherwise abnormally high serum potassium levels, and relieved the muscular damage. At the cellular level, WP[6] reversed the Sch induced depolarization and reduced the efflux of intracellular potassium. Conclusion: Synthetic receptors, particularly WP[6], exhibited high binding affinities towards Sch, and presented a significant potential as supramolecular therapeutics to treat the various side effects of Sch by specifically sequestering Sch in vivo .

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Section: Discussionmentioning

confidence: 99%

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent

Zhang

Qian

et al. 2019

Theranostics

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“…Compounds belonging to these subgroups also exhibit varying additional activities. This classification is presented in Table 2 [1][2][3][24][25][26][27][28][29][30][31]. Aminosteroid drugs can induce vagolytic activity, leading to tachycardia and hypertension.…”

Section: Characteristic Of Non-depolarizing Muscle Relaxantsmentioning

confidence: 99%

The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms

Radkowski,

Szewczyk,

Czajka

et al. 2024

Med Sci Monit

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Muscle relaxants have broad application in anesthesiology. They can be used for safe intubation, preparing the patient for surgery, or improving mechanical ventilation. Muscle relaxants can be classified based on their mechanism of action into depolarizing and non-depolarizing muscle relaxants and centrally acting muscle relaxants. Non-depolarizing neuromuscular blocking drugs (NMBDs) (eg, tubocurarine, atracurium, pipecuronium, mivacurium, pancuronium, rocuronium, vecuronium) act as competitive antagonists of nicotine receptors. By doing so, these drugs hinder the depolarizing effect of acetylcholine, thereby eliminating the potential stimulation of muscle fibers. Depolarizing drugs like succinylcholine and decamethonium induce an initial activation (depolarization) of the receptor followed by a sustained and steady blockade. These drugs do not act as competitive antagonists; instead, they function as more enduring agonists compared to acetylcholine itself. Many factors can influence the duration of action of these drugs. Among them, electrolyte disturbances and disruptions in acid-base balance can have an impact. Acidosis increases the potency of non-depolarizing muscle relaxants, while alkalosis induces resistance to their effects. In depolarizing drugs, acidosis and alkalosis produce opposite effects. The results of studies on the impact of acid-base balance disturbances on non-depolarizing relaxants have been conflicting. This work is based on the available literature and the authors' experience. This article aimed to review the use of anesthetic muscle relaxants in patients with acid-base disturbances.

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“…Hence, this potential drug combination has attracted attention as a possible alternative to succinylcholine [ 81 , 82 ]. In addition, calabadion, a new antagonist of benzylisoquinoline-based neuromuscular blocking agent, and a combination of gantacurium (CW002) and L-cysteine are anticipated to become part of future ECT procedures [ 83 ].…”

Section: Drugs For Ectmentioning

confidence: 99%

Anesthetic care for electroconvulsive therapy

et al. 2022

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Counselling and medication are often thought of as the only interventions for psychiatric disorders, but electroconvulsive therapy (ECT) has also been applied in clinical practice for over 80 years. ECT refers to the application of an electric stimulus through the patient’s scalp to treat psychiatric disorders such as treatment-resistant depression, catatonia, and schizophrenia. It is a safe, effective, and evidence-based therapy performed under general anesthesia with muscle relaxation. An appropriate level of anesthesia is essential for safe and successful ECT; however, little is known about this because of the limited interest from anesthesiologists. As the incidence of ECT increases, more anesthesiologists will be required to better understand the physiological changes, complications, and pharmacological actions of anesthetics and adjuvant drugs. Therefore, this review focuses on the fundamental physiological changes, management, and pharmacological actions associated with various drugs, such as anesthetics and neuromuscular blocking agents, as well as the comorbidities, indications, contraindications, and complications of using these agents as part of an ECT procedure through a literature review and our own experiences.

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New Drug Developments for Neuromuscular Blockade and Reversal: Gantacurium, CW002, CW011, and Calabadion

Cited by 14 publications

References 23 publications

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent

Supramolecular therapeutics to treat the side effects induced by a depolarizing neuromuscular blocking agent

The Influence of Acid-Base Balance on Anesthetic Muscle Relaxants: A Comprehensive Review on Clinical Applications and Mechanisms

Anesthetic care for electroconvulsive therapy

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