Literature DB >> 18072133

Reactivation of sarin-inhibited pig brain acetylcholinesterase using oxime antidotes.

Kamil Kuca1, Daniel Jun.   

Abstract

INTRODUCTION: Organophosphorus nerve agents inhibit the enzyme, acetylcholinesterase (AChE; EC 3.1.1.7). AChE reactivators (also known as oximes) are generally used for the reactivation of an inhibited enzyme.
METHODS: Two new AChE reactivators--K033 and K027--were tested for their in vitro reactivation of sarin-inhibited pig-brain AChE. Their reactivation potencies were compared with the commercially available AChE reactivators, pralidoxime, obidoxime, and HI-6.
RESULTS: Of the oximes tested, the newly developed oxime K027 achieved the highest reactivation potency (100%; concentration of the oxime -10(-2) M). However, oxime HI-6 (33%) and obidoxime (23%) seem to be the best AChE reactivators for human relevant doses (10(-4) M and lower).
CONCLUSION: For human relevant doses, newly developed oximes (K027 and K033) do not surpass the reactivation potency of the most promising oxime, HI-6.

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Year:  2006        PMID: 18072133      PMCID: PMC3550075          DOI: 10.1007/bf03161181

Source DB:  PubMed          Journal:  J Med Toxicol        ISSN: 1556-9039


  27 in total

Review 1.  Organophosphates/nerve agent poisoning: mechanism of action, diagnosis, prophylaxis, and treatment.

Authors:  Jirí Bajgar
Journal:  Adv Clin Chem       Date:  2004       Impact factor: 5.394

Review 2.  Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents.

Authors:  J Kassa
Journal:  J Toxicol Clin Toxicol       Date:  2002

3.  Ion channel blockade by oximes and recovery of diaphragm muscle from soman poisoning in vitro.

Authors:  J E Tattersall
Journal:  Br J Pharmacol       Date:  1993-04       Impact factor: 8.739

4.  Reactivation kinetics of acetylcholinesterase from different species inhibited by highly toxic organophosphates.

Authors:  F Worek; G Reiter; P Eyer; L Szinicz
Journal:  Arch Toxicol       Date:  2002-07-12       Impact factor: 5.153

5.  A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods.

Authors:  J Kassa; J Cabal
Journal:  Pharmacol Toxicol       Date:  1999-01

6.  In vitro reactivation of tabun-inhibited acetylcholinesterase using new oximes--K027, K005, K033 and K048.

Authors:  K Kuca; J Cabal
Journal:  Cent Eur J Public Health       Date:  2004-03       Impact factor: 1.163

7.  A comparison of the ability of a new bispyridinium oxime--1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide and currently used oximes to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods.

Authors:  K Kuca; J Kassa
Journal:  J Enzyme Inhib Med Chem       Date:  2003-12       Impact factor: 5.051

8.  Synthesis, biological activity, and docking studies of new acetylcholinesterase inhibitors of the bispyridinium type.

Authors:  Petra Kapková; Nikolaus Stiefl; Ulf Sürig; Bernd Engels; Knut Baumann; Ulrike Holzgrabe
Journal:  Arch Pharm (Weinheim)       Date:  2003-11       Impact factor: 3.751

9.  Protection by butyrylcholinesterase against organophosphorus poisoning in nonhuman primates.

Authors:  C A Broomfield; D M Maxwell; R P Solana; C A Castro; A V Finger; D E Lenz
Journal:  J Pharmacol Exp Ther       Date:  1991-11       Impact factor: 4.030

10.  The influence of oxime and anticholinergic drug selection on the potency of antidotal treatment to counteract acute toxic effects of tabun in mice.

Authors:  Jirí Kassa
Journal:  Neurotox Res       Date:  2006-01       Impact factor: 3.911

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