Comparison of in vitro potency of oximes (pralidoxime, obidoxime, HI-6) to reactivate sarin-inhibited acetylcholinesterase in various parts of pig brain

• Published in: Journal of applied toxicology Vol. 25; no. 4; pp. 271 - 276
• Main Authors: Kuca, Kamil, Cabal, Jiri, Kassa, Jiri, Jun, Daniel, Hrabinová, Martina
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01-07-2005; Wiley
• Subjects: acetylcholinesterase; Acetylcholinesterase - metabolism; Animals; Biological and medical sciences; brain; Brain - drug effects; Brain - enzymology; Chemical and industrial products toxicology. Toxic occupational diseases; Cholinesterase Inhibitors - pharmacology; Cholinesterase Reactivators - pharmacology; Gas, fumes; HI-6; in vitro; Kinetics; Male; Medical sciences; obidoxime; Obidoxime Chloride - pharmacology; Oximes; pig; pig, brain; pralidoxime; Pralidoxime Compounds - pharmacology; Pyridinium Compounds - pharmacology; sarin; Sarin - pharmacology; Swine; Toxicology; Enzyme inducer; Cholinesterase reactivator; brain; in vitro; Central nervous system; Oxime; Esterases; Acetylcholinesterase; Encephalon; Chemical warfare agent; Sarin; sarin; acetylcholinesterase; pralidoxime; obidoxime; HI-6; pig; Ungulata; Toxic gas; Enzyme; In vitro; Cholinesterase; Carboxylic ester hydrolases; Pig; Vertebrata; Mammalia; Pralidoxime iodide; Hydrolases; Organophosphorus compounds; Artiodactyla; Antidote; Obidoxime chloride
• ISSN: 0260-437X; 1099-1263
• DOI: 10.1002/jat.1053

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. Copyright © 2005 John Wiley & Sons. Ltd.