Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes.
BACKGROUND
Organophosphorus nerve agents inhibit the enzyme, acetylcholinesterase (AChE; EC 3.1.1.7). AChE reactivators (also known as oximes) are generally used for the reactivation of an inhibited enzyme.


METHODS
Two new AChE reactivators--K033 and K027--were tested for their in vitro reactivation of sarin-inhibited pig-brain AChE. Their reactivation potencies were compared with the commercially available AChE reactivators, pralidoxime, obidoxime, and HI-6.


RESULTS
Of the oximes tested, the newly developed oxime K027 achieved the highest reactivation potency (100%; concentration of the oxime -10(-2) M). However, oxime HI-6 (33%) and obidoxime (23%) seem to be the best AChE reactivators for human relevant doses (10(-4) M and lower).


CONCLUSIONS
For human relevant doses, newly developed oximes (K027 and K033) do not surpass the reactivation potency of the most promising oxime, HI-6.
Kuca
Kamil
K
Centre of Advanced Studies, Department of Toxicology, Faculty Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Jun
Daniel
D
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D009768:Obidoxime Chloride / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012107:Research Design; D012524:Sarin / Q000633:toxicity*; D013552:Swine
C489959:1,4-bis(2-hydroxyiminomethylpyridinium)butane; C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; D000931:Antidotes; 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