A comparison of reactivating efficacy of newly developed oximes (K074, K075) and currently available oximes (obidoxime, HI-6) in soman, cyclosarin and tabun-poisoned rats.
The potency of newly developed oximes (K074, K075) and commonly used oximes (obidoxime, HI-6) to reactivate nerve agent-inhibited acetylcholinesterase was evaluated in rats poisoned with soman, tabun or cyclosarin at a lethal dose corresponding to their LD(50) value. In vivo determined percentage of reactivation of soman-inhibited blood and brain acetylcholinesterase in poisoned rats showed that only the oxime HI-6 was able to reactivate soman-inhibited acetylcholinesterase in the peripheral (blood) as well as central (brain) compartment. In vivo determined percentage of reactivation of tabun-inhibited blood and brain acetylcholinesterase in poisoned rats showed that obidoxime is the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the peripheral compartment (blood) while K074 seems to be the most efficacious reactivator of tabun-inhibited acetylcholinesterase among studied oximes in the central compartment (brain). In vivo determined percentage of reactivation of cyclosarin-inhibited blood and brain acetylcholinesterase in poisoned rats showed that HI-6 is the most efficacious reactivator of cyclosarin-inhibited acetylcholinesterase among studied oximes. Due to their reactivating effects, 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 soman and cyclosarin poisonings.
Kassa
Jiri
J
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Jun
Daniel
D
Karasova
Jana
J
Bajgar
Jiri
J
Kuca
Kamil
K
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D002619:Chemical Warfare Agents / Q000506:poisoning*; D004793:Enzyme Reactivators / Q000494:pharmacology*; D008297:Male; D062025:Organophosphate Poisoning; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012999:Soman / Q000506:poisoning*
D002619:Chemical Warfare Agents; D004793:Enzyme Reactivators; D010755:Organophosphates; D009943:Organophosphorus Compounds; D010091:Oximes; D012999:Soman; D000110:Acetylcholinesterase; C009374:tabun; C053914:cyclohexyl methylphosphonofluoridate