title: Comparison of reactivating and therapeutic efficacy of two salts of the oxime HI-6 against tabun, soman and cyclosarin in rats.
abstract: The reactivating and therapeutic efficacy of two salts of the oxime HI-6 (dichloride and dimethanesulphonate) against chosen nerve agents (tabun, soman and cyclosarin) was compared in rats. The potency of both salts of HI-6 to decrease the acute toxicity of tabun, soman and cyclosarin was similar in nerve agent-poisoned rats. While the potency of HI-6 dichloride and HI-6 dimethanesulphonate to counteract acute toxic effects of tabun is rather low, both salts of HI-6 were able to decrease the acute toxicity of soman two times and acute toxicity of cyclosarin more than three times. The therapeutic efficacy of both salts of the oxime HI-6 corresponds to their reactivating potency. While the reactivating efficacy of HI-6 dichloride as well as HI-6 dimethanesulphonate against tabun was negligible, their potency to reactivate soman-inhibited acetylcholinesterase and cyclosarin-inhibited acetylcholinesterase in peripheral (blood) and central (brain) compartment was relatively high. HI-6 dichloride showed a somewhat higher potency to reactivate tabun-inhibited acetylcholinesterase in brain, and soman-inhibited acetylcholinesterase in blood and brain than HI-6 dimethanesulphonate but the differences were not significant. Thus, the replacement of dichloride anion by dimethanesulphonate anion in the oxime HI-6 does not influence the therapeutic and reactivating efficacy of the oxime HI-6 against nerve agents. In addition, the higher solubility and stability of HI-6 dimethanesulphonate in comparison with HI-6 dichloride makes it possible to increase the dose and thus, the effectiveness of the oxime HI-6 in the antidotal treatment of acute nerve agent poisonings.
authors.affiliation: Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Trebresska 1575, 500 01 Hradec Kralove, Czech Republic. kassa@pmfhk.cz
authors.forename: Jiri
authors.initials: J
authors.lastname: Kassa
authors.forename: Daniel
authors.initials: D
authors.lastname: Jun
authors.forename: Kamil
authors.initials: K
authors.lastname: Kuca
authors.forename: Jiri
authors.initials: J
authors.lastname: Bajgar
mesh_terms: D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000627:therapeutic use*; D007928:Lethal Dose 50; D008297:Male; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010755:Organophosphates / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D009943:Organophosphorus Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010091:Oximes; D011726:Pyridinium Compounds / Q000737:chemistry / Q000627:therapeutic use*; D051381:Rats; D012999:Soman / Q000037:antagonists & inhibitors* / Q000633:toxicity*
chemical_list: D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D018727:Muscarinic Antagonists; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D001285:Atropine; D012999:Soman; C022870:asoxime chloride; C009374:tabun; C053914:cyclohexyl methylphosphonofluoridate