In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases.
In this work, two oximes for the treatment of tabun-inhibited acetylcholinesterase (AChE; EC 3.1.1.7), K074 (1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide) and K075 ((E)-1,4-bis(4-hydroxyiminomethylpyridinium)but-2-en dibromide), were tested in vitro as reactivators of AChE. Comparison was made with currently used AChE reactivators (pralidoxime, HI-6, methoxime and obidoxime). Human brain homogenate was taken as an appropriate source of the cholinesterases. As resulted, oxime K074 appears to be the most potent reactivator of tabun-inhibited AChE, with reactivation potency comparable to that of obidoxime. A second AChE reactivator, K075, does not attain as great a reactivation potency as K074, although its maximal reactivation (17%) was achieved at relevant concentrations for humans.
Kuca
Kamil
K
Centre of Advanced Studies, and Department of Toxicology, Faculty of Military Health Sciences, University of Defense, Trebesska 1575, 500 01 Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Cabal
Jiri
J
Jun
Daniel
D
Musilek
Kamil
K
D000110:Acetylcholinesterase / Q000378:metabolism*; D002073:Butanes / Q000737:chemistry / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D009768:Obidoxime Chloride / Q000737:chemistry / Q000494:pharmacology; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000737:chemistry / Q000494:pharmacology*; D011220:Pralidoxime Compounds / Q000737:chemistry / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000737:chemistry / Q000494:pharmacology*
C515196:1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide; D002073:Butanes; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; C518856:K075 compound; D010755:Organophosphates; D010091:Oximes; D011220:Pralidoxime Compounds; D011726:Pyridinium Compounds; D009768:Obidoxime Chloride; C005514:N,N'-monomethylenebis(pyridiniumaldoxime); D000110:Acetylcholinesterase; C022870:asoxime chloride; C028797:pralidoxime; C009374:tabun