A comparison of reactivating and therapeutic efficacy of the oxime K203 and its fluorinated analog (KR-22836) with currently available oximes (obidoxime, trimedoxime, HI-6) against tabun in rats and mice.
The potency of newly developed bispyridinium compound K203 and its fluorinated analog KR-22836 in reactivating tabun-inhibited acetylcholinesterase and reducing tabun-induced lethal toxic effects was compared with commonly used oximes (obidoxime, trimedoxime, the oxime HI-6) using in vivo methods. Studies determining the percentage of reactivation of tabun-inhibited blood and tissue acetylcholinesterase in rats showed that the reactivating efficacy of K203 is higher than the reactivating efficacy of its fluorinated analog KR-22836 as well as currently available oximes studied. The therapeutic efficacy of the oxime K203 and its fluorinated analog corresponds to their potency to reactivate tabun-inhibited acetylcholinesterase. According to the results, the oxime K203 is more suitable than KR-22836 for the replacement of commonly used oximes for the antidotal treatment of acute tabun poisoning due to its relatively high potency to counteract the acute toxicity of tabun.
Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove, Czech Republic. kassa@pmfhk.cz
Jiri
J
Kassa
Jana Zdarova
JZ
Karasova
Filip
F
Caisberger
Kamil
K
Musilek
Kamil
K
Kuca
Young-Sik
YS
Jung
D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D002801:Cholinesterase Reactivators / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009768:Obidoxime Chloride / Q000494:pharmacology / Q000627:therapeutic use; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology* / Q000627:therapeutic use; D011726:Pyridinium Compounds / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014289:Trimedoxime / Q000494:pharmacology / Q000627:therapeutic use
C524716:1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)but-2-ene; D000931:Antidotes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D014289:Trimedoxime; C022870:asoxime chloride; C009374:tabun