Naslov
Evaluation of oxime K203 as antidote in tabun poisoning

Autori
Kovarik, Zrinka ; Lucić Vrdoljak, Ana ; Berend, Suzana ; Katalinić, Maja ; Kuča, Kamil ; Musilek, Kamil ; Radić, Božica

Izvornik
Arhiv za higijenu rada i toksikologiju (0004-1254) 60 (2009), 1; 19-26

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
acetylcholinesterase ; bioscavenger ; butyrylcholinesterase ; K048 ; nerve agents ; TMB-4 ; pyridinium oxime

Sažetak
We studied bispyridinium oxime K203 [(E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyimino methylpyridinium)- but-2-ene dibromide] with tabun-inhibited human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in vitro, and its antidotal effect on tabun-poisoned mice and rats in vivo. We compared it with oximes K048 and TMB-4, which have proven the most effi cient oxime antidotes in tabun poisoning by now. Tabun-inhibited AChE was completely reactivated by K203, with the overall reactivation rate constant of 1806 L mol-1 min-1. This means that K203 is a very potent reactivator of tabun-inhibited AChE. In addition, K203 reversibly inhibited AChE (Ki = 0.090 mmol L-1) and BChE (Ki = 0.91 mmol L-1), and exhibited its protective effect against phosphorylation of AChE by tabun in vitro. In vivo, a quarter of the LD50 K203 dose insured survival of all mice after the application of as many as 8 LD50 doses of tabun, which is the highest dosage obtained compared to K048 and TMB-4. Moreover, K203 showed high therapeutic potency in tabun-poisoned rats, preserving cholinesterase activity in rat plasma up to 60 min after poisoning. This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

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