title: A comparison of the potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to counteract tabun-induced neurotoxicity in rats.
abstract: The neuroprotective effects of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in combination with atropine in rats poisoned with tabun at a sublethal dose (180 micro g/kg i.m.; 80% LD(50)) were studied. The tabun-induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24h and 7 days following tabun challenge. The results indicate that all oximes studied in combination with atropine allow all tabun-poisoned rats to survive within 7 days following tabun challenge while two non-treated tabun-poisoned rats died within 2h. Both newly developed oximes combined with atropine seem to be effective antidotes for a decrease in tabun-induced neurotoxicity in the case of sublethal poisoning although they are not able to eliminate tabun-induced neurotoxicity completely. The oxime K075 showed a higher neuroprotective efficacy against tabun than K074 according to the number of eliminated tabun-induced neurotoxic signs at 24h as well as 7 days after tabun challenge. The neuroprotective efficacy of obidoxime in combination with atropine is similar to the potency of newly developed oxime K075 but the ability of the oxime HI-6 to counteract tabun-induced acute neurotoxicity is significantly lower at 24h as well as 7 days after tabun poisoning. Due to their neuroprotective effects, both newly developed oximes (especially K075) appear to be more suitable oximes for the antidotal treatment of acute tabun poisonings than the oxime HI-6.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, 500 01 Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Jana
authors.initials: J
authors.lastname: Karasova
mesh_terms: D000818:Animals; D000931:Antidotes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D001285:Atropine / Q000494:pharmacology / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects; D002073:Butanes / Q000494:pharmacology / Q000627:therapeutic use*; D002619:Chemical Warfare Agents / Q000633:toxicity; D018680:Cholinergic Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D007273:Injections, Intramuscular; D007765:Lacrimal Apparatus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D015877:Miosis / Q000517:prevention & control; D015394:Molecular Structure; D009129:Muscle Tonus / Q000187:drug effects; D020258:Neurotoxicity Syndromes / Q000209:etiology / Q000517:prevention & control*; D009768:Obidoxime Chloride / Q000494:pharmacology / Q000627:therapeutic use*; D010755:Organophosphates / Q000008:administration & dosage / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013666:Tears / Q000378:metabolism; D013997:Time Factors; D018675:Toxicity Tests / Q000379:methods; D016896:Treatment Outcome
chemical_list: C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; D000931:Antidotes; D002073:Butanes; D002619:Chemical Warfare Agents; D018680:Cholinergic Antagonists; C518856:K075 compound; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D001285:Atropine; C022870:asoxime chloride; C009374:tabun