The benefit of combination of oximes for the neuroprotective efficacy of antidotal treatment of sarin-poisoned rats.

Abstract

The potency of the oxime HI-6 and two combinations of oximes (HI-6 + trimedoxime, HI-6 + K203) to reduce sarin-induced acute neurotoxic signs and symptoms was evaluated in this study. Sarin-induced neurotoxicity and the neuroprotective effects of atropine alone or in combination with HI-6 alone and HI-6 combined with trimedoxime or K203 in rats poisoned with sarin at a sublethal dose (108 μg/kg i.m.; 90% of LD(50) value) were monitored by a functional observatory battery (FOB) 24 h following sarin administration. The results indicate that both mixtures of oximes combined with atropine were able to survive sarin-poisoned rats 24 h following sarin administration while two non-treated sarin-poisoned rats and one sarin-poisoned rat treated with atropine alone or with atropine in combination with the oxime HI-6 died within 24 h following sarin poisoning. All types of antidotal treatment were able to decrease sarin-induced neurotoxic signs and symptoms but not completely. While atropine alone and atropine in combination with the oxime HI-6 were able to eliminate some sarin-induced neurotoxic signs and symptoms, the neuroprotective efficacy of both combinations of oximes with atropine was slightly higher. Thus, both tested combinations of oximes in combination with atropine bring a small benefit for the neuroprotective efficacy of antidotal treatment of acute sarin poisonings.

• Authors: Jiri Kassa, Gabriela Kunesova
• Journal: Toxicology mechanisms and methods (Toxicol Mech Methods) Vol. 22 Issue 4 Pg. 260-7 (May 2012) ISSN: 1537-6524 [Electronic] England
• PMID: 22149934 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

• Animals
• Antidotes (administration & dosage, therapeutic use)
• Atropine (chemistry)
• Chemical Warfare Agents (poisoning, toxicity)
• Cholinesterase Inhibitors (poisoning, toxicity)
• Cholinesterase Reactivators (administration & dosage, therapeutic use)
• Drug Therapy, Combination
• Male
• Molecular Structure
• Neuroprotective Agents (therapeutic use)
• Oximes (administration & dosage, chemistry, therapeutic use)
• Pyridinium Compounds (administration & dosage, chemistry, therapeutic use)
• Rats
• Rats, Wistar
• Sarin (poisoning, toxicity)
• Trimedoxime (administration & dosage, chemistry, therapeutic use)