Reactivation of organophosphate-inhibited acetylcholinesterase by quaternary pyridinium aldoximes.
We investigated the relationship between the chemical structure of acetylcholinesterase (AChE; EC 3.1.1.7) reactivators and their potency in reactivating this enzyme, after prior inhibition by VX (O-ethyl-S-(2-diisopropylaminoethyl)-methylthiophosphonate), tabun, sarin, and cyclosarin. The oximes, pralidoxime (2-PAM), HI-6 [1-(2-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium)-2-oxa-propane dichloride], obidoxime and HS-6 [1-(2-hydroxyiminomethylpyridinium)-3-(3-carbamoylpyridinium)-2-oxa-propane dichloride] were used as representatives of the group of AChE reactivators. Rat brain AChE was used as the appropriate source of the enzyme. Our results confirm that there is no single broad-spectrum oxime suitable for the treatment of poisoning with all highly toxic organophosphorus agents.
Kuca
Kamil
K
Purkyne Medical Military Academy, Department of Toxicology, Hradec Králové, Czech Republic. kucakam@pmfhk.cz
Patocka
Jirí
J
Cabal
Jirí
J
Jun
Daniel
D
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D002801:Cholinesterase Reactivators / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D010755:Organophosphates / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D051381:Rats
D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D000110:Acetylcholinesterase