| Title : Evaluation of oxime k203 as antidote in tabun poisoning - Kovarik_2009_Arh.Hig.Rada.Toksikol_60_19 |
| Author(s) : Kovarik Z , Vrdoljak AL , Zunec S , Katalinic M , Kuc K , Musilek K , Radic B |
| Ref : Arh Hig Rada Toksikol , 60 :19 , 2009 |
| Abstract : We studied bispyridinium oxime K203 [(E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-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 efficient 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 (K(i) = 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. |
| ESTHER : Kovarik_2009_Arh.Hig.Rada.Toksikol_60_19 |
| PubMedSearch : Kovarik_2009_Arh.Hig.Rada.Toksikol_60_19 |
| PubMedID: 19329372 |
Kovarik Z, Vrdoljak AL, Zunec S, Katalinic M, Kuc K, Musilek K, Radic B (2009)
Evaluation of oxime k203 as antidote in tabun poisoning
Arh Hig Rada Toksikol
60 :19
Kovarik Z, Vrdoljak AL, Zunec S, Katalinic M, Kuc K, Musilek K, Radic B (2009)
Arh Hig Rada Toksikol
60 :19