Currently used cholinesterase reactivators against nerve agent intoxication: comparison of their effectivity in vitro.
In vitro comparison of reactivation efficacy of five currently used oximes - pralidoxime, obidoxime, trimedoxime, methoxime, and HI-6 (at two concentrations: 10-5 and 10-3 M) - against acetylcholinesterase (AChE; E.C. 3.1.1.7) inhibited by six different nerve agents (VX, Russian VX, sarin, cyclosarin, tabun, soman) and organophosphorus insecticide chlorpyrifos was the aim of this study. As a source of AChE in the experiments, rat brain homogenate was used. According to the results obtained, no AChE reactivator was able to reach sufficient potency for AChE inhibited by all nerve agents used. Moreover, oxime HI-6 (the most effective one) was not able to reactivate tabun- and soman-inhibited AChE. Due to this fact, it could be designated as a partially broad-spectrum reactivator.
Kuca
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Jun
Daniel
D
Bajgar
Jiri
J
D000818:Animals; D001921:Brain / Q000201:enzymology; D002619:Chemical Warfare Agents / Q000737:chemistry / Q000633:toxicity*; D004390:Chlorpyrifos / Q000737:chemistry / Q000633:toxicity; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D009768:Obidoxime Chloride / Q000737:chemistry / Q000494:pharmacology; D010755:Organophosphates / Q000737:chemistry / Q000633:toxicity; D009943:Organophosphorus Compounds / Q000737:chemistry / Q000633:toxicity; D009946:Organothiophosphorus Compounds / Q000737:chemistry / Q000633:toxicity; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology; D011220:Pralidoxime Compounds / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012524:Sarin / Q000737:chemistry / Q000633:toxicity; D012999:Soman / Q000737:chemistry / Q000633:toxicity; D014020:Tissue Extracts; D014289:Trimedoxime / Q000737:chemistry / Q000494:pharmacology
D002619:Chemical Warfare Agents; D004390:Chlorpyrifos; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D009768:Obidoxime Chloride; D010755:Organophosphates; D009943:Organophosphorus Compounds; D009946:Organothiophosphorus Compounds; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D012524:Sarin; D012999:Soman; D014020:Tissue Extracts; D014289:Trimedoxime; C005514:N,N'-monomethylenebis(pyridiniumaldoxime); C009680:VX-agent; C022870:asoxime chloride; C028797:pralidoxime; C009374:tabun; C053914:cyclohexyl methylphosphonofluoridate