title: 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.affiliation: Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Jan
authors.initials: J
authors.lastname: Misik
authors.forename: Jana Zdarova
authors.initials: JZ
authors.lastname: Karasova
mesh_terms: D000818:Animals; D000931:Antidotes / Q000009:adverse effects / Q000627:therapeutic use*; D001285:Atropine / Q000627:therapeutic use; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D002619:Chemical Warfare Agents / Q000737:chemistry / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000009:adverse effects / Q000627:therapeutic use*; D018153:Czech Republic; D004359:Drug Therapy, Combination; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000627:therapeutic use; D009474:Neurons / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000188:drug therapy* / Q000503:physiopathology; D009768:Obidoxime Chloride / Q000009:adverse effects / Q000627:therapeutic use*; D010091:Oximes / Q000009:adverse effects / Q000627:therapeutic use*; D011597:Psychomotor Performance / Q000187:drug effects; D011726:Pyridinium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000037:antagonists & inhibitors* / Q000633:toxicity
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; D012524:Sarin; C022870:asoxime chloride