Reactivation of organophosphate‐inhibited human AChE by combinations of obidoxime and HI 6 in vitro

@article{Worek2007ReactivationOO,
  title={Reactivation of organophosphate‐inhibited human AChE by combinations of obidoxime and HI 6 in vitro},
  author={Franz Worek and Nadine Aurbek and Horst Thiermann},
  journal={Journal of Applied Toxicology},
  year={2007},
  volume={27}
}
Highly toxic organophosphorus‐type (OP) chemical warfare agents (nerve agents) and OP pesticides may be used by terrorists and during military conflicts emphasizing the necessity for the development of effective medical countermeasures. The standard treatment with atropine and acetylcholinesterase (AChE) reactivators (oximes) is considered to be ineffective with certain nerve agents due to low oxime efficacy. Despite research over decades none of the oximes has turned out to be a broad spectrum… Expand
Reactivation of nerve agent-inhibited human acetylcholinesterase by obidoxime, HI-6 and obidoxime+HI-6: Kinetic in vitro study with simulated nerve agent toxicokinetics and oxime pharmacokinetics.
TLDR
It is indicated that a combination of obidoxime and HI-6 would be beneficial for the treatment of poisoning by a broad spectrum of nerve agents and could present an interim solution until more effective and broad-spectrum reactivators are available. Expand
Organophosphorus compounds and oximes: a critical review
TLDR
A critical analysis is called for of the value of oximes as mainstay of treatment as well as the potential and limitations of established and novel reactivators in human OP pesticide poisoning. Expand
Design, evaluation and structure—Activity relationship studies of the AChE reactivators against organophosphorus pesticides
TLDR
This review is the summarized design, evaluation, and structure–activity relationship studies of recently produced AChE reactivators against OPP, and several novel compounds show very promising abilities as comparable to commercial oximes. Expand
Effect of reversible ligands on oxime-induced reactivation of sarin- and cyclosarin-inhibited human acetylcholinesterase.
TLDR
The results of the present study did not confirm that AChE-ligands directly accelerate the reactivation of OP-inhibited A cholinesterase by oximes, but indirectly by prevention of re-inhibition by the reaction product POX. Expand
Tabun-inhibited rat tissue and blood cholinesterases and their reactivation with the combination of trimedoxime and HI-6 in vivo.
TLDR
In rats poisoned with tabun and treated with combination of atropine and different doses of trimedoxime and HI-6, changes of acetylcholinesterase activities were studied and suggest that the action of combination of oximes in vivo is different from that observed in vitro. Expand
Reactivation potency of the acetylcholinesterase reactivator obidoxime is limited.
TLDR
It was found that obidoxime could not be termed as universal antidote or if its reactivation potency in case of some organophosphorus inhibitors is limited. Expand
Comparative protective effects of HI-6 and MMB-4 against organophosphorous nerve agent poisoning.
TLDR
HI-6 has been demonstrated to be generally a superior reactivator of nerve agent inhibited enzyme, particularly with human and non-human primate derived enzyme, and has also shown better protective effects against the lethality of most OP agents in a variety of species. Expand
Optimal choice of acetylcholinesterase reactivators for antidotal treatment of nerve agent intoxication.
TLDR
It was clearly demonstrated that reactivation potency ofHI-6 DMS in comparison with HI-6 Cl in vivo was the same and bioavailability of HI- 6 DMS is better than that of HI -6 Cl. Expand
The value of novel oximes for treatment of poisoning by organophosphorus compounds.
TLDR
The unsatisfying situation calls for studies with standardized and comparable experimental conditions in order to allow a sound assessment of available and novel oximes and an interim solution may be the combination of two oximes with overlapping reactivation spectrum. Expand
Two possibilities how to increase the efficacy of antidotal treatment of nerve agent poisonings.
TLDR
The review describes the evaluation of the potency of newly developed oximes or combinations of oximes to reactivate nerve agent-inhibited acetylcholinesterase and to counteract the acute toxicity of nerve agents in comparison with single commonly used oxime. Expand
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