Evaluation of the neuroprotective efficacy of newly developed oximes (K206, K269) and currently available oximes (obidoxime, HI-6) in cyclosarin-poisoned rats

Basic Clin Pharmacol Toxicol. 2009 Mar;104(3):228-35. doi: 10.1111/j.1742-7843.2008.00352.x. Epub 2008 Dec 25.

Abstract

The neuroprotective effects of newly developed oximes (K206, K269) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with cyclosarin were studied. The cyclosarin-induced neurotoxicity was monitored using a functional observational battery at 24 hr following cyclosarin challenge. The results indicate that a newly developed oxime K206 is able to counteract cyclosarin-induced neurotoxicity while the neuroprotective potency of another newly developed oxime (K269) is negligible. The neuroprotective efficacy of K206 is markedly higher than commonly used obidoxime; nevertheless, its potency to eliminate cyclosarin-induced neurotoxicity is slightly lower compared to the oxime HI-6. Thus, a newly developed oxime K206 seems to be a better oxime for the antidotal treatment of cyclosarin poisonings than obidoxime due to higher neuroprotective potency although the oxime HI-6 is still the most suitable oxime for the antidotal treatment of acute poisonings with cyclosarin.

Publication types

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

MeSH terms

  • Animals
  • Antidotes / pharmacology
  • Atropine
  • Chemical Warfare Agents / poisoning
  • Cholinesterase Reactivators / pharmacology
  • Drug Therapy, Combination
  • Male
  • Muscarinic Antagonists / pharmacology
  • Neuroprotective Agents / pharmacology
  • Obidoxime Chloride / pharmacology*
  • Organophosphate Poisoning
  • Organophosphorus Compounds
  • Oximes / pharmacology*
  • Pyridinium Compounds / pharmacology*
  • Rats
  • Rats, Wistar

Substances

  • 1-(3-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene
  • 1-(4-(1-aminohydroxyiminomethyl)pyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene
  • Antidotes
  • Chemical Warfare Agents
  • Cholinesterase Reactivators
  • Muscarinic Antagonists
  • Neuroprotective Agents
  • Organophosphorus Compounds
  • Oximes
  • Pyridinium Compounds
  • Obidoxime Chloride
  • Atropine
  • asoxime chloride
  • cyclohexyl methylphosphonofluoridate