Novel acetylcholinesterase reactivator--oxime K048--reactivation activity in vitro.
A novel acetylcholinesterase (AChE) reactivator, a bispyridinium aldoxime named K048, was first synthesized in 2003. It is a promising antidote against tabun poisoning. Afterwards, other studies on several cholinesterases (ChE) of different species (humans, rats, etc.) and models (in vitro or in vivo) were conducted. We tested this oxime against nine different AChE inhibitors using in vitro tests on rat brain homogenate as source of enzyme. Our results showed that oxime K048 reached promising reactivation activity in case of all tested AChE inhibitors, except cyclosarin, at oxime concentration 10(-3) M. At a concentration of 10(-5) M, which is more common for human use, only methylchlorpyrifos-inhibited AChE was reactivated.
Kuca
Kamil
K
Center of Advanced Studies, Faculty of Military Health Sciences, University of Defence, Hradec Kralove, Czech Republic. kucakam@pmfhk.cz
Marek
Jan
J
Karasova
Jana
J
Pohanka
Miroslav
M
Korabecny
Jan
J
Kalasz
Huba
H
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002619:Chemical Warfare Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004793:Enzyme Reactivators / Q000494:pharmacology*; D006801:Humans; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
C488676:1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane; D000931:Antidotes; D002619:Chemical Warfare Agents; D002800:Cholinesterase Inhibitors; D004793:Enzyme Reactivators; D009943:Organophosphorus Compounds; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase