Interaction of pyridinium oximes with acetylcholinesterase and their effect on organophosphate-poisoned mice.
The progressive inhibition of acetylcholinesterase (AChE [EC 3.1.1.7]) by organophosphates (OPs), such as the nerve agents tabun and soman, is due to phosphorylation of the active center serine characterized by the formation of conjugates and inactivation of this essential enzyme involved in neurotransmission. Presently, a combination of an antimuscarinic agent, e.g., atropine, and an AChE reactivator, oxime, is used for the treatment of organophosphorus compound poisoning. The increased concern about terrorist use of nerve agents prompted us to search for new, more effective oximes against tabun and soman poisoning. We investigated the interactions of five bispyridinium oximes with human erythrocyte AChE and their effects on tabun- and soman-poisoned mice.
Kovarik
Zrinka
Z
Institute for Medical Research and Occupational Health, POB 291, HR-10001 Zagreb, Croatia. zkovarik@imi.hr
Calić
Maja
M
Vrdoljak
Ana Lucić
AL
Radić
Bozica
B
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism*; D000818:Animals; D000931:Antidotes / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004912:Erythrocytes / Q000201:enzymology; D006801:Humans; D051379:Mice; D010755:Organophosphates / Q000633:toxicity*; D010091:Oximes / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D012999:Soman / Q000633:toxicity
D000931:Antidotes; D002800:Cholinesterase Inhibitors; D010755:Organophosphates; D010091:Oximes; D011726:Pyridinium Compounds; D012999:Soman; D000110:Acetylcholinesterase; C009374:tabun