A comparison of the potency of a novel bispyridinium oxime K203 and currently available oximes (obidoxime, HI-6) to counteract the acute neurotoxicity of sarin in rats.

Abstract

The neuroprotective effects of a newly developed oxime K203 and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with sarin were studied. The sarin-induced neurotoxicity was monitored using a functional observatory battery at 2 hr after sarin challenge. The results indicate that the potency of a novel bispyridinium oxime K203 to counteract sarin-induced neurotoxicity is relatively low and roughly corresponds to the neuroprotective efficacy of obidoxime. Among tested oximes, the oxime HI-6 seems to be significanlty more efficacious to counteract acute neurotoxicity of sarin than commonly used obidoxime and a newly developed oxime K203. Thus, the oxime K203 does not provide any beneficial effect for the antidotal treatment of acute poisoning with sarin in comparison with the oxime HI-6 that should be considered to be the best oxime for antidotal treatment of acute sarin poisonings.

• Authors: Jiri Kassa, Jan Misik, Jana Zdarova Karasova
• Journal: Basic & clinical pharmacology & toxicology (Basic Clin Pharmacol Toxicol) Vol. 111 Issue 5 Pg. 333-8 (Nov 2012) ISSN: 1742-7843 [Electronic] England
• PMID: 22536919 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.

Chemical References

• 1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene
• Antidotes
• Chemical Warfare Agents
• Cholinesterase Inhibitors
• Cholinesterase Reactivators
• Muscarinic Antagonists
• Oximes
• Pyridinium Compounds
• Obidoxime Chloride
• Atropine
• Sarin
• asoxime chloride

Topics

• Animals
• Antidotes (adverse effects, therapeutic use)
• Atropine (therapeutic use)
• Autonomic Nervous System (drug effects, physiopathology)
• Chemical Warfare Agents (chemistry, toxicity)
• Cholinesterase Inhibitors (chemistry, toxicity)
• Cholinesterase Reactivators (adverse effects, therapeutic use)
• Czech Republic
• Drug Therapy, Combination
• Lethal Dose 50
• Male
• Muscarinic Antagonists (therapeutic use)
• Neurons (drug effects)
• Neurotoxicity Syndromes (drug therapy, physiopathology)
• Obidoxime Chloride (adverse effects, therapeutic use)
• Oximes (adverse effects, therapeutic use)
• Psychomotor Performance (drug effects)
• Pyridinium Compounds (adverse effects, therapeutic use)
• Rats
• Rats, Wistar
• Sarin (antagonists & inhibitors, toxicity)