title: A comparison of neuroprotective efficacy of two novel reactivators of acetylcholinesterase called K920 and K923 with the oxime K203 and trimedoxime in tabun-poisoned rats.
abstract: The ability of two newly developed bispyridinium oximes (K920, K923) to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the oxime K203 and trimedoxime using a functional observational battery (FOB). The neuroprotective effects of the oximes studied combined with atropine on rats poisoned with tabun at a sublethal dose (130 μg/kg i.m.; 80% of LD50value) were evaluated. Tabun-induced neurotoxicity was monitored by FOB at 2 h after tabun administration. The results indicate that all tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment while one non-treated tabun-poisoned rat died within 2 h. Both newly developed oximes (K920, K923) combined with atropine were able to markedly decrease tabun-induced neurotoxicity in the case of sublethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. Their ability to decrease tabun-induced acute neurotoxicity did not prevail the neuroprotective efficacy of trimedoxime and the oxime K203. Therefore, the newly developed oximes are not suitable for the replacement of currently available oximes (especially trimedoxime) in the treatment of acute tabun poisonings.
authors.affiliation: a Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , University of Defense , Hradec Kralove , Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.affiliation: a Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , University of Defense , Hradec Kralove , Czech Republic.
authors.forename: Jan
authors.initials: J
authors.lastname: Misik
authors.affiliation: a Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , University of Defense , Hradec Kralove , Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Hatlapatkova
authors.affiliation: a Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences , University of Defense , Hradec Kralove , Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zdarova Karasova
mesh_terms: D000818:Animals; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000627:therapeutic use*; D008297:Male; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000737:chemistry / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000737:chemistry / Q000627:therapeutic use*; D017208:Rats, Wistar; D014289:Trimedoxime / Q000737:chemistry / Q000627:therapeutic use*
chemical_list: C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D002801:Cholinesterase Reactivators; C000621356:K920 compound; C000621357:K923 compound; D018696:Neuroprotective Agents; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; C009374:tabun
keywords: K920; K923; Tabun; functional observational battery; neurotoxicity; rats