Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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In vitro Evaluation of New Acetylcholinesterase Reactivators as Casual Antidotes against Tabun and Cyclosarin

  • Kuca, Kamil (Department of Toxicology, Faculty of Military Health Sciences) ;
  • Jun, Daniel (Department of Toxicology, Faculty of Military Health Sciences) ;
  • Kim, Tae-Hyuk (Medicinal Science Division, Korea Research Institute of Chemical Technology) ;
  • Cabal, Jiri (Department of Toxicology, Faculty of Military Health Sciences) ;
  • Jung, Young-Sik (Medicinal Science Division, Korea Research Institute of Chemical Technology)
  • Published : 2006.03.20
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Abstract

Nerve agents (sarin, tabun, soman and VX) are class of military important substances able to cause many severe intoxications during few minutes. Currently, the threat of misuse of these agents is daily discussed. Unfortunately, there is no single antidote able to treat intoxication caused by all of these agents. Owing to this fact, new generation of antidotes, especially acetylcholinesterase (AChE; EC 3.1.1.7) reactivators, is still developed. In this study, we have tested four newly developed AChE reactivators: 1-(4-hydroxyiminomethylpyridinium)- 5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (1), 1-(3-hydroxyiminomethylpyridinium)-5-(4-carbamoylpyridinium)-3-oxa-pentane dibromide (2), 1,5-bis(2-hydroxyiminomethylpyridinium)-3-oxa-pentane dichloride (3) and 1,5-bis(4-hydroxyiminomethylpyridinium)-3-oxa-pentane dibromide (4) for their potency to reactivate in vitro tabun and cyclosarin-inhibited AChE. Their reactivation efficacy was compared with currently the most promising oxime HI-6 (1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride). According to obtained results, two AChE reactivators 1 and 4 were able to reactivate tabun-inhibited AChE. On the contrary, there was no better AChE reactivator than HI-6 able to reactivate cyclosarin-inhibited AChE.

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