title: A comparison of neuroprotective efficacy of the oxime K203 and its fluorinated analogue (KR-22836) with obidoxime in Tabun-poisoned rats.
abstract: The ability of the newly developed bispyridinium compound K203 and its fluorinated analogue KR-22836 to reduce tabun-induced acute neurotoxic signs and symptoms was compared with the currently available reactivator of acetylcholinesterase-obidoxime. Tabun-induced neurotoxicity and the neuroprotective effects of all tested oximes in combination with atropine in rats poisoned with tabun at a sublethal dose (200 μg/kg intramuscularly (i.m.); 80% of LD(50) value) were monitored by a functional observational battery at 24 hr after tabun challenge. The results indicate that all tested oximes combined with atropine were able to survive tabun-poisoned rats 24 hr after tabun challenge while one non-treated tabun-poisoned rat died within 24 hr after tabun poisoning. All tested oximes combined with atropine were able to decrease tabun-induced neurotoxicity in the case of sublethal poisoning but they did not eliminate all tabun-induced acute neurotoxic signs and symptoms. While the ability to reduce tabun-induced acute neurotoxicity of obidoxime and K203 was similar, the neuroprotective efficacy of KR-22836 was slightly higher compared to other tested oximes. Thus, the newly developed fluorinated analogue of K203, called KR-22836, is able to slightly increase the neuroprotective effectiveness of antidotal treatment of acute tabun poisonings compared to K203 and currently available obidoxime.
authors.affiliation: Department of Toxicology, 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: Sandra
authors.initials: S
authors.lastname: Tesarova
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Young-Sik
authors.initials: YS
authors.lastname: Jung
mesh_terms: D000208:Acute Disease; D000818:Animals; D001341:Autonomic Nervous System / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D002619:Chemical Warfare Agents / Q000506:poisoning*; D006948:Hyperkinesis / Q000139:chemically induced / Q000517:prevention & control; D008297:Male; D015394:Molecular Structure; D009129:Muscle Tonus / Q000187:drug effects; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009768:Obidoxime Chloride / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D016896:Treatment Outcome
chemical_list: C574701:1-(4-carbamoylpyridinium)-4-(3-fluoro-4-hydroxyiminomethylpyridinium)-but-2-ene; C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D002619:Chemical Warfare Agents; D018696:Neuroprotective Agents; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; C009374:tabun