title: The evaluation of the reactivating and therapeutic efficacy of two novel oximes (K361 and K378) in comparison with the oxime K203 and trimedoxime in tabun-poisoned rats and mice.
abstract: The potency of two newly developed oximes (K361 and K378) to reactivate tabun-inhibited cholinesterase and to reduce acute toxicity of tabun was compared with the oxime K203 and trimedoxime using in vivo methods. The study determining percentage of reactivation of tabun-inhibited diaphragm cholinesterase in poisoned rats showed that the reactivating efficacy of the oxime K378 is slightly lower than the reactivating potency of the oxime K203 and trimedoxime while the ability of the oxime K361 to reactivate tabun-inhibited cholinesterase is markedly lower compared with the oxime K203 and trimedoxime. In the brain, the potency of both newly developed oximes to reactivate tabun-inhibited cholinesterase was negligible. The therapeutic efficacy of both newly developed oximes roughly corresponds to their weak reactivating efficacy. Their potency to reduce acute toxicity of tabun was significantly lower compared with the oxime K203 as well as trimedoxime. In conclusion, the reactivating and therapeutic potency of both newly developed oximes does not prevail the effectiveness of the oxime K203 and trimedoxime and, therefore, they are not suitable for their replacement of commonly used oximes for the treatment of acute tabun poisoning.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, Trebesska, Hradec Kralove , Czech Republic.
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Vendula
authors.initials: V
authors.lastname: Sepsova
authors.forename: Martina
authors.initials: M
authors.lastname: Tumova
authors.forename: Kamil
authors.initials: K
authors.lastname: Musilek
authors.forename: Anna
authors.initials: A
authors.lastname: Horova
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000627:therapeutic use*; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014289:Trimedoxime / Q000627:therapeutic use*
chemical_list: C000593470:1-(3-phenylpropyl)-4-hydroxyiminomethylpyridinium; C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; C000593469:4-(1-amino-1-hydroxyiminomethyl)-4'-hydroxyiminomethyl-1,1'-(but-1,4-diyl)bispyridinium; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; C009374:tabun