Bispyridinium oximes as antidotal treatment of cyclosarin poisoning-in vitro and in vivo testing.

Abstract	The mechanism of intoxication with organophosphorus compounds, including highly toxic nerve agents and less toxic pesticides, is based on the formation of irreversibly inhibited acetylcholinesterase, which causes cumulation of neuromediator acetylcholine in synaptic clefts and subsequent overstimulation of cholinergic receptors, that is followed by a generalized cholinergic crisis. Nerve agent poisoning is conventionally treated using a combination of a cholinolytic (atropine mostly) to counteract the accumulation of acetylcholine and acetylcholinesterase reactivators (pralidoxime or obidoxime) to reactivate inhibited acetylcholinesterase. In this study of cyclosarin poisoning treatment, oximes of different chemical structures (obidoxime, HI-6, BI-6, and HS-6) were tested in vitro on rat brain acetylcholinesterase (enzyme source: rat brain homogenate), and afterwards, they were tested in vivo in equimolar doses, in mice and rats. The HI-6 oxime appeared to be the most effective oxime in vitro and in vivo.
Authors	Lucie Bartosova, Kamil Kuca, Daniel Jun, Gabriela Kunesova
Journal	International journal of toxicology (Int J Toxicol) 2005 Nov-Dec Vol. 24 Issue 6 Pg. 399-402 ISSN: 1091-5818 [Print] United States
PMID	16393932 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Antidotes BI 6 Cholinesterase Inhibitors Cholinesterase Reactivators Enzyme Inhibitors Muscarinic Antagonists Organophosphorus Compounds Oximes Pyridinium Compounds Obidoxime Chloride Atropine asoxime chloride cyclohexyl methylphosphonofluoridate
Topics	Animals Antidotes (pharmacology, therapeutic use) Atropine (therapeutic use) Brain (drug effects, enzymology) Cholinesterase Inhibitors (toxicity) Cholinesterase Reactivators (pharmacology, therapeutic use) Dose-Response Relationship, Drug Drug Evaluation, Preclinical Enzyme Inhibitors (toxicity) Female In Vitro Techniques Kinetics Lethal Dose 50 Mice Muscarinic Antagonists (therapeutic use) Obidoxime Chloride (pharmacology, therapeutic use) Organophosphorus Compounds (toxicity) Oximes (pharmacology, therapeutic use) Pyridinium Compounds (pharmacology, therapeutic use) Rats Rats, Wistar

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