Comparison of in vitro potency of oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited acetylcholinesterase in various parts of pig brain.
The potency of currently used oximes to reactivate sarin-inhibited acetylcholinesterase (AChE) in various parts of pig brain and whole pig brain was evaluated using in vitro methods. Significant differences in reactivation potency among all tested oximes were observed. At concentrations (10(-4) M) corresponding to recommended doses in vivo, the oxime HI-6 seems to be a more efficacious reactivator of sarin-inhibited AChE in whole pig brain as well as in cerebral hemispheres and cerebellum compared with the other oximes studied. Nevertheless, there are not any differences in the potency of oximes tested to reactivate sarin-inhibited AChE in medulla oblongata. Thus, the oxime HI-6 appears to be the most promising oxime among currently available oximes for the antidotal treatment of acute sarin poisoning, although it is not more efficacious than other currently used oximes in medulla oblongata, whose function is necessary for the vital functions of respiration and circulation.
Kuca
Kamil
K
Department of Toxicology, Faculty of Military Health Sciences, PO Box 35/T, 500 01, Hradec Králové, Czech Republic.
Cabal
Jiri
J
Kassa
Jiri
J
Jun
Daniel
D
Hrabinová
Martina
M
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D009768:Obidoxime Chloride / Q000494:pharmacology*; D010091:Oximes; D011220:Pralidoxime Compounds / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012524:Sarin / Q000494:pharmacology*; D013552:Swine
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; D012524:Sarin; D000110:Acetylcholinesterase; C022870:asoxime chloride; C028797:pralidoxime