A comparison of the reactivating and therapeutic efficacy of chosen combinations of oximes with individual oximes against VX in rats and mice.
The ability of 2 combinations of oximes (HI-6 + trimedoxime and HI-6 + K203) to reactivate VX-inhibited acetylcholinesterase and reduce acute toxicity of VX was compared with the reactivating and therapeutic efficacy of antidotal treatment involving a single oxime (HI-6, trimedoxime, K203) in rats and mice. Our results showed that the reactivating efficacy of both combinations of oximes studied in rats is significantly higher than the reactivating efficacy of all individual oximes in diaphragm and roughly corresponds to the most effective individual oxime in blood and brain. Both combinations of oximes were found to be more effective in the reduction of acute lethal toxicity of VX in mice than the antidotal treatment involving the most efficacious individual oxime although the difference is not significant. Based on the obtained data, we can conclude that the antidotal treatment involving the chosen combinations of oximes brings benefit for the reactivation of VX-inhibited acetylcholinesterase in rats and for the antidotal treatment of VX-induced acute poisoning in mice.
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Jiri
J
Kassa
Jana Zdarova
JZ
Karasova
Vendula
V
Sepsova
Filip
F
Caisberger
Jiri
J
Bajgar
D000110:Acetylcholinesterase / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001285:Atropine / Q000494:pharmacology; D001921:Brain / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009946:Organothiophosphorus Compounds / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014289:Trimedoxime / Q000494:pharmacology*
D000110:Acetylcholinesterase; D000931:Antidotes; D001285:Atropine; D002800:Cholinesterase Inhibitors; D004338:Drug Combinations; D009946:Organothiophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D014289:Trimedoxime; C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; C009680:VX-agent; C022870:asoxime chloride