title: Evaluation of the neuroprotective efficacy of newly developed oximes (K206, K269) and currently available oximes (obidoxime, HI-6) in cyclosarin-poisoned rats.
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.
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: Jana Zdarova
authors.initials: JZ
authors.lastname: Karasova
authors.forename: Jiri
authors.initials: J
authors.lastname: Bajgar
authors.forename: Sandra
authors.initials: S
authors.lastname: Tesarova
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
mesh_terms: D000818:Animals; D000931:Antidotes / Q000494:pharmacology; D001285:Atropine; D002619:Chemical Warfare Agents / Q000506:poisoning; D002801:Cholinesterase Reactivators / Q000494:pharmacology; D004359:Drug Therapy, Combination; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009768:Obidoxime Chloride / Q000494:pharmacology*; D062025:Organophosphate Poisoning; D009943:Organophosphorus Compounds; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C534465:1-(3-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene; C534466:1-(4-(1-aminohydroxyiminomethyl)pyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene; D000931:Antidotes; D002619:Chemical Warfare Agents; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; C022870:asoxime chloride; C053914:cyclohexyl methylphosphonofluoridate