A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in soman, cyclosarin and tabun-poisoned rats

Chem Biol Interact. 2008 Sep 25;175(1-3):425-7. doi: 10.1016/j.cbi.2008.05.001. Epub 2008 May 4.

Abstract

The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to reactivate nerve agent-inhibited acetylcholinesterase was evaluated in rats poisoned with soman, tabun or cyclosarin at a lethal dose corresponding to their LD(50) value. In vivo determined percentage of reactivation of soman-inhibited blood and brain acetylcholinesterase in poisoned rats showed that only the oxime HI-6 was able to reactivate soman-inhibited acetylcholinesterase in the peripheral (blood) as well as central (brain) compartment. In vivo determined percentage of reactivation of tabun-inhibited blood and brain acetylcholinesterase in poisoned rats showed that obidoxime is the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the peripheral compartment (blood) while K074 seems to be the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the central compartment (brain). In vivo determined percentage of reactivation of cyclosarin-inhibited blood and brain acetylcholinesterase in poisoned rats showed that HI-6 is the most efficacious reactivator of cyclosarin-inhibited acetylcholinesterase among studied oximes. Due to their reactivating effects, both newly developed K oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisonings while the oxime HI-6 is still the most promising oxime for the treatment of acute soman and cyclosarin poisonings.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism
  • Animals
  • Chemical Warfare Agents / poisoning*
  • Enzyme Reactivators / pharmacology*
  • Male
  • Organophosphate Poisoning*
  • Organophosphates
  • Organophosphorus Compounds
  • Oximes / pharmacology*
  • Rats
  • Rats, Wistar
  • Soman / poisoning*

Substances

  • Chemical Warfare Agents
  • Enzyme Reactivators
  • Organophosphates
  • Organophosphorus Compounds
  • Oximes
  • Soman
  • Acetylcholinesterase
  • tabun
  • cyclohexyl methylphosphonofluoridate