title: The Evaluation of the Potency of Newly Developed Oximes (K727, K733) and Trimedoxime to Counteract Acute Neurotoxic Effects of Tabun in Rats.
abstract: OBJECTIVE
  The ability of two newly developed oximes (K727, K733) to reduce tabun-induced acute neurotoxic signs and symptoms was evaluated and compared with currently available trimedoxime in rats.
  
  
  METHODS
  The neuroprotective effects of the oximes studied combined with atropine on Wistar rats poisoned with tabun at a lethal dose (380 µg/kg i.m.; 90% of LD50 value) were evaluated. Tabun-induced neurotoxicity was monitored by the functional observational battery consisting of 38 measurements of sensory, motor and autonomic nervous functions at 2 hours following tabun challenge.
  
  
  RESULTS
  All tested oximes combined with atropine enable tabun-poisoned rats to survive till the end of experiment. Both newly developed oximes (K727, K733) combined with atropine were able to decrease tabun-induced neurotoxicity in the case of lethal poisoning although they did not eliminate all tabun-induced acute neurotoxic signs and symptoms.
  
  
  CONCLUSIONS
  The ability of both novel bispyridinium oximes to decrease tabun-induced acute neurotoxicity was slightly lower than that of trimedoxime. Therefore, the newly developed oximes are not suitable for the replacement of commonly used oximes such as trimedoxime in the treatment of acute tabun poisonings.
authors.affiliation: Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Hradec Králové, Czech Republic. kassa@pmfhk.cz.
authors.forename: Jiří
authors.initials: J
authors.lastname: Kassa
authors.affiliation: Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Hradec Králové, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Hatlapatková
authors.affiliation: Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences, University of Defense, Hradec Králové, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Žďárová Karasová
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology; D062025:Organophosphate Poisoning / Q000188:drug therapy / Q000209:etiology; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014289:Trimedoxime / Q000494:pharmacology*
chemical_list: C000604114:4-(ethylcarboxyl)-2'-(hydroxyiminomethyl)-1,1'-(phenylene-1,3-diyl)-bispyridinium; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D018696:Neuroprotective Agents; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; C000604113:naphthylene-2,7-diyl-bis(2-hydroxyiminomethylpyridinium); D014289:Trimedoxime; D001285:Atropine; C009374:tabun
keywords: Functional observational battery; Neurotoxicity; Oximes; Rats; Tabun