title: A comparison of the efficacy of new asymmetric bispyridinium oximes (K027, K048) with currently available oximes against tabun by in vivo methods.
abstract: The potency of newly developed asymmetric bispyridinium oximes (K027, K048) in reactivating tabun-inhibited acetylcholinesterase (AChE) and in eliminating tabun-induced acute toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determined the percent of reactivation of tabun-inhibited blood and tissue AChE in poisoned rats and showed that the reactivating efficacy of both newly developed oximes is comparable with obidoxime and trimedoxime, the most efficacious known reactivators of tabun-inhibited AChE. These were also found to be sufficiently efficacious in the elimination of acute lethal toxic effects in tabun-poisoned rats. The oxime HI-6, relatively efficacious against soman, did not seem to be an adequately effective oxime in reactivation of tabun-inhibited AChE and in counteracting acute lethal effects of tabun. In addition, our results confirm that the efficacy of oximes in reactivating tabun-inhibited AChE in blood, diaphragm, and brain correlates with the potency of oximes in protecting rats poisoned with supralethal doses of tabun.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, Hradec Králové, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Cabal
authors.forename: Martin
authors.initials: M
authors.lastname: Paar
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000506:poisoning*; D003964:Diaphragm / Q000201:enzymology; D004789:Enzyme Activation; D008297:Male; D062025:Organophosphate Poisoning; D010755:Organophosphates; D010091:Oximes / Q000494:pharmacology*; D011041:Poisoning / Q000188:drug therapy; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D002619:Chemical Warfare Agents; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase; C009374:tabun