Bisquaternary oximes as reactivators of tabun-inhibited human brain cholinesterases: an in vitro study.
Intoxications caused by tabun nerve agent are generally very hard to treat by convential acetylcholinesterase (AChE) reactivators. Due to this, new AChE reactivators are still developed. In this study, we have tested three new promising bisquaternary AChE reactivators: K027, K033 and K048. These reactivators were previously tested on rat brain homogenate. To mimic reality, we studied the potency of these new oximes to reactivate tabun-inhibited human brain cholinesterases. As is evident from the results, reactivator K048 (reactivation 40%) surpassed all reactivators tested in this study [including the most promising ones, namely trimedoxime (37%) and obidoxime (33%)]. Moreover, if compared to our previous results from rat brain studies, species differences were demonstrated.
Kuca
Kamil
K
Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Jun
Daniel
D
Cabal
Jiri
J
Musilova
Lucie
L
D001921:Brain / Q000201:enzymology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology / Q000627:therapeutic use*; D011726:Pyridinium Compounds / Q000494:pharmacology*
C489959:1,4-bis(2-hydroxyiminomethylpyridinium)butane; C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; C009374:tabun