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  • We studied bispyridinium oxime K203 with tabun-inhibited human AChE and 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. This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development.
  • We studied bispyridinium oxime K203 with tabun-inhibited human AChE and 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. This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development. (en)
Title
  • Evaluation of oxime K203 as antidote in tabun poisoning
  • Evaluation of oxime K203 as antidote in tabun poisoning (en)
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  • Evaluation of oxime K203 as antidote in tabun poisoning
  • Evaluation of oxime K203 as antidote in tabun poisoning (en)
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  • RIV/60162694:G44__/09:00002423!RIV11-MO0-G44_____
http://linked.open...avai/riv/aktivita
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  • N
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  • 1
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  • 313895
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  • RIV/60162694:G44__/09:00002423
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  • acetylcholinesterase; bioscavenger; butyrylcholinesterase; K048; nerve agents; TMB-4; pyridinium oxime (en)
http://linked.open.../riv/klicoveSlovo
http://linked.open...odStatuVydavatele
  • HR - Chorvatská republika
http://linked.open...ontrolniKodProRIV
  • [D0C2D4B02747]
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  • Archives of Industrial Hygiene and Toxicology
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http://linked.open...UplatneniVysledku
http://linked.open...v/svazekPeriodika
  • 60
http://linked.open...iv/tvurceVysledku
  • Kuča, Kamil
  • Musílek, Kamil
  • Berend, S.
  • Radic, B.
  • Kovarik, Zrinka
  • Calic, M.
  • Lucic Vrdoljak, A.
issn
  • 0004-1254
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http://localhost/t...ganizacniJednotka
  • G44
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