Functional basis for dose-dependent antagonism of rat and rabbit neuromuscular transmission by the bis-pyridinium oxime MMB4

Machamer, James B.; Apland, James P.; Winner, Brittany; Wolfe, Sarah E; Pagarigan, Kathleen T.; Bounader, Kevin M; Kasten, Shane A.; Adler, Michaël; McNutt, Patrick

doi:10.1007/s00204-020-02858-4

Cited by 4 publications

(3 citation statements)

References 60 publications

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“…Methoxime, or MMB-4, is a bis-pyridinium oxime that has shown improved pharmaceutical properties and therapeutic range compared to 2-PAM and obidoxime ( Lundy et al, 2011 ; Machamer et al, 2020 ). In addition, Asoxime Chloride (HI-6) is a substantially broad-spectrum AChE reactivator, and a double-positive charged bispyridinium compound, commonly used in Canada, Sweden, and the Czech Republic.…”

Section: Methodsmentioning

confidence: 99%

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

et al. 2023

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Background: The whole world has learned about the existence of a highly toxic neuro-paralytic substance called Novichok. A wide range of neuro-paralytic toxins were used during the wars of decades ago, which also had harmful and irreversible effects. Fortunately, the establishment of conventions prohibiting the use of these weapons prevented the adverse clinical consequences of these compounds. What we did in the present study was to evaluate the clinical features of Novichok, how to manage exposure to it, and to evaluate the prognostic aspects associated with this poisoning agent.Methods: The manuscript especial databases including Medline, Web of knowledge, Google scholar, and Scopus were deeply searched by the two blinded investigators for all eligible studies based on the considered keywords. Initially 98 articles were initially collected by database searching that considering eligibility criteria, 83 articles were finally eligible for the final assessment. There is a lack of clinical trials and case-cohort studies on general population about treatment and side effects when it comes to human nerve agents and most of the data in our search is based on animal studies.Results: In evaluating various clinical, auto physiological and prognostic aspects of exposure to these substances, special attention was necessary to the following points. First, Novichok agents are considered more potent than other toxic agents. Pathophysiologically, these agents irreversibly bind acetylcholinesterase and produce a rapid cholinergic toxidrome which is responsible for the clinical manifestations as well as the potential dangerous and life threatening side effects caused by these agents. Uniquely, these agents are thought to also target every neuron in the central and peripheral nervous system. As a managerial and therapeutic approach, early and timely treatment of its related complication along with prevents massive exposure and decontamination in addition to rapid resuscitation can prohibit debilitating neuropathy and death due to facing it.Conclusion: The present review highlights the importance of recognizing the potential acute toxic effects of Novichok agents, diagnostic and therapeutic approaches (life-saving antidotal therapy) to complications and ultimately the application of guidelines to improve the prognosis of exposure to these agents for both victims and medical community.

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Section: Methodsmentioning

confidence: 99%

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

et al. 2023

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“…This double positive charged bis-pyridinium compound has been shown to be effective in the treatment of neural factors [ 48 , 49 ]. A bis-pyridinium oxime with superior therapeutic and pharmaceutical properties compared to both obidoxime and 2-PAM is a methoxime (MMB-4) [ 50 ]. An oxime with restricted use due to CNS and hepatotoxic side effects is thimodexime bromide (TMB-4) despite its effectiveness in reactivating AChE [ 51 ].…”

Section: Treatment Of Novichok Exposure: Where To Start?mentioning

confidence: 99%

Review of Possible Therapies in Treatment of Novichoks Poisoning and HAZMAT/CBRNE Approaches: State of the Art

Noga¹,

Michalska²,

Jurowski

2023

JCM

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Novichoks-organophosphorus compounds belong to the nerve agents group, constituting the fourth generation of chemical warfare agents. The tremendous toxicity of Novichoks is assumed to be several times greater than that of VX, whereas no published experimental research supports this. They were surreptitiously created during the Cold War by the Soviet Union. Novichok’s toxic action mechanism consists of the inhibition of acetylcholinesterase activity. The review includes data on treating poisoning caused by OPs which could be used as guidelines for the therapy in case of Novichok exposure and HAZMAT/CBRNE approaches. Novichoks pose a severe threat due to their toxicity; however, there is insufficient information about the identity of A-series nerve agents. Filling in the missing data gaps will accelerate progress in improving protection against Novichoks and developing optimal therapy for treating poisoning casualties. Furthermore, introducing solutions to protect medical personnel in contact with a hazardous substance increases the chances of saving casualties of HAZMAT/CBRNE incidents.

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“…Since 2018, in the toxicological literature, the following lines of investigation can be identified, which are reflected by key contributions to Archives of Toxicology. Clinical reports (Novichok) and improvement of therapy of intoxications by organophosphorus compounds (Hulse et al 2019 ; Steindl et al 2021 ; Vale et al 2018 ; Worek et al 2020 ; Zandona et al 2020 , 2021 ): a special focus is development of novel antidotes, e.g., novel oximes (Machamer et al 2020 ; Zandona et al 2020 , 2021 ) or engineered phoshotriesterases (Stigler et al 2021 ). Given the world-wide incidents attributed to chemical weapons, such as Novichok agents, intensive-care clinicians should know how to rapidly recognize symptoms of acute poisoning and to administer life-saving antidotal therapy, when indicated (Chai et al 2018 ).…”

mentioning

confidence: 99%

Recent research on Novichok

Bolt

Hengstler

2022

Arch Toxicol

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Functional basis for dose-dependent antagonism of rat and rabbit neuromuscular transmission by the bis-pyridinium oxime MMB4

Cited by 4 publications

References 60 publications

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

A complete, evidence-based review on novichok poisoning based on epidemiological aspects and clinical management

Review of Possible Therapies in Treatment of Novichoks Poisoning and HAZMAT/CBRNE Approaches: State of the Art

Recent research on Novichok

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