In vitro reactivation of tabun-inhibited acetylcholinesterase using new oximes--K027, K005, K033 and K048.
Four new AChE oximes for reactivation of acetylcholinesterase inhibited with tabun - K027 [1-(4-hydroxyiminomethylpyridinium)-3-(4-carbamoylpyridinium) propane dibromide], K005 [1,3-bis(2-hydroxyiminomethylpyridinium) propane dibromide], K033 [1,4-bis(2-hydroxyiminomethylpyridinium) butane dibromide] and K048 [1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium) butane dibromide] were prepared. Their efficacies to reactivate tabun-inhibited acetylcholinesterase were studied and compared with the currently used acetylcholinesterase reactivators (pralidoxime, obidoxime and HI-6). Reactivator K048 seems to be promising reactivator of tabun-inhibited AChE. Its reactivation potency is significantly higher than the efficacy of HI-6 and pralidoxime, and comparable with the potency of the obidoxime at human relevant doses.
Kuca
K
K
Department of Toxicology, Purkynĕ Medical Military Academy, Hradec Králové, Czech Republic. kucakam@pmfhk.cz
Cabal
J
J
D000818:Animals; D001921:Brain / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D002801:Cholinesterase Reactivators / Q000138:chemical synthesis / Q000494:pharmacology*; D066298:In Vitro Techniques; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats
C489957:1,3-bis(2-hydroxyiminomethylpyridinium)propane; C489959:1,4-bis(2-hydroxyiminomethylpyridinium)butane; C481758:1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium) propane dibromide; D002800:Cholinesterase Inhibitors; D002801:Cholinesterase Reactivators; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; C009374:tabun