A comparison of the potency of newly developed oximes (K074, K075) and currently available oximes (obidoxime, trimedoxime, HI-6) to counteract acute toxic effects of tabun and cyclosarin in mice.
The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, trimedoxime, and HI-6) to counteract tabun or cyclosarin-induced acute toxic effects was studied in mice. The therapeutic efficacy of trimedoxime and both newly developed oximes (K074, K075) was significantly higher than the potency of obidoxime and the oxime HI-6 in the case of acute tabun poisonings. On the other hand, the oxime HI-6 was significantly more efficacious than other studied oximes when mice were intoxicated with cyclosarin. The findings support the hypothesis that the therapeutic efficacy of oximes depends on the type of nerve agent. Due to their therapeutic efficacy, both newly developed K oximes can be considered to be promising oximes for the antidotal treatment of acute tabun poisonings, while the oxime HI-6 is still the most promising oxime for the treatment of acute cyclosarin poisonings due to its high potency to counteract cyclosarin-induced acute toxic effects.
Kassa
Jirí
J
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic.
Humlicek
Vojtech
V
D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001285:Atropine / Q000494:pharmacology* / Q000627:therapeutic use; D002073:Butanes / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000506:poisoning*; D002801:Cholinesterase Reactivators / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D009768:Obidoxime Chloride / Q000494:pharmacology; D062025:Organophosphate Poisoning; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D011041:Poisoning / Q000188:drug therapy; D011726:Pyridinium Compounds / Q000494:pharmacology; D014289:Trimedoxime / Q000494:pharmacology
C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; D000931:Antidotes; D002073:Butanes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; C518856:K075 compound; D018727:Muscarinic Antagonists; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D014289:Trimedoxime; D001285:Atropine; C022870:asoxime chloride; C009374:tabun; C053914:cyclohexyl methylphosphonofluoridate