Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo

Bajgar, Jiří; Karasová, Jana Žďárová; Kassa, Jiřı́; Cabal, Jiřı́; Fusek, J.; Blaha, V.; Tesarova, Sandra

doi:10.1016/j.cbi.2010.02.009

Cited by 9 publications

(5 citation statements)

References 20 publications

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“…17 ) were developed in 1950s, and primarily intended to reduce the nerve agents intoxication [148]. Additionally, some of them exerted good effects in the restoration of inhibited cholinesterases by OP insecticides as well [149].…”

Section: Detoxification Of Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

et al. 2013

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Acetylcholinesterase is involved in the termination of impulse transmission by rapid hydrolysis of the neurotransmitter acetylcholine in numerous cholinergic pathways in the central and peripheral nervous systems. The enzyme inactivation, induced by various inhibitors, leads to acetylcholine accumulation, hyperstimulation of nicotinic and muscarinic receptors, and disrupted neurotransmission. Hence, acetylcholinesterase inhibitors, interacting with the enzyme as their primary target, are applied as relevant drugs and toxins. This review presents an overview of toxicology and pharmacology of reversible and irreversible acetylcholinesterase inactivating compounds. In the case of reversible inhibitors being commonly applied in neurodegenerative disorders treatment, special attention is paid to currently approved drugs (donepezil, rivastigmine and galantamine) in the pharmacotherapy of Alzheimer’s disease, and toxic carbamates used as pesticides. Subsequently, mechanism of irreversible acetylcholinesterase inhibition induced by organophosphorus compounds (insecticides and nerve agents), and their specific and nonspecific toxic effects are described, as well as irreversible inhibitors having pharmacological implementation. In addition, the pharmacological treatment of intoxication caused by organophosphates is presented, with emphasis on oxime reactivators of the inhibited enzyme activity administering as causal drugs after the poisoning. Besides, organophosphorus and carbamate insecticides can be detoxified in mammals through enzymatic hydrolysis before they reach targets in the nervous system. Carboxylesterases most effectively decompose carbamates, whereas the most successful route of organophosphates detoxification is their degradation by corresponding phosphotriesterases.

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Section: Detoxification Of Acetylcholinesterase Inhibitorsmentioning

confidence: 99%

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

et al. 2013

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“…Perhaps, development of some more universal oxime with broader potency could be a future solution. On the contrary, such broader activity could be attained by the two oximes combination [26].…”

Section: Resultsmentioning

confidence: 88%

On THE UNIVERSALITY OF OXIME HLö-7 - ANTIDOTE FOR CASE OF THE NERVE AGENT POISONING

Kuča¹,

Musílek²,

Karasová³

et al. 2011

Mil. Med. Sci. Lett.

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Searching for the universal oxime, which could be able to reactivate acetylcholinesterase inhibited by various nerve agents is still topic of high interest. In this contribution, oxime HLö-7, that was thoroughly discussed in the last decade, is evaluated. Its universality was tested in vitro using the rat brain homogenate as a source of the cholinesterases. The main members of the nerve agent family (tabun, sarin, soman, cyclosarin and VX) were used for this purpose. As shown, oxime HLö-7 was able to reactivate cholinesterases inhibited by all tested nerve agents with the exception of tabun. Hence, it could not be designated as the broad-spectrum reactivator.

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“…-some other drugs and approaches are under experimental studies -e.g. huperzine A (Bajgar et al 2007a), combinations of reactivators (Bajgar et al 2010;, and new reactivators (Kassa et al 2007(Kassa et al , 2008(Kassa et al , 2009Kuca et al 2010;Musilek et al 2010a,b).…”

Section: Discussionmentioning

confidence: 99%

From the Research of Cholinesterase Reactivators to the Effective Therapy of Organophosphate/Nerve Agent Poisoning

Bajgar¹,

Kassa²

2012

Mil. Med. Sci. Lett.

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The aim of this study is to inform about different techniques used to improve treatment of nerve agents intoxication at the Department of Toxicology. METHODS: Different methods are briefly mentioned and their importance for development of more effective reactivators is discussed. RESULTS: Basic characterization of nerve agents and therapeutic drugs is necessary after literature survey. Usage of different techniques and properties of various reactivators are studied and, on this basis, the most effective ones are tested in details and proposed for practical use. CONCLUSIONS: The results described in this study clearly demonstrate that for the development of new and more effective cholinesterase reactivators, a complex approach using different methodical attitudes is necessary.

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Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo

Cited by 9 publications

References 20 publications

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

Acetylcholinesterase Inhibitors: Pharmacology and Toxicology

On THE UNIVERSALITY OF OXIME HLö-7 - ANTIDOTE FOR CASE OF THE NERVE AGENT POISONING

From the Research of Cholinesterase Reactivators to the Effective Therapy of Organophosphate/Nerve Agent Poisoning

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