Specification of the structure of oximes able to reactivate tabun-inhibited acetylcholinesterase

Basic & Clinical Pharmacology & Toxicology
Jirí CabalJ Kassa

Abstract

The efficacy of various oximes to reactivate acetylcholinesterase phosphorylated by tabun (O-ethyl-N,N-dimethyl phosphoramidocyanidate) was tested by in vitro and in vivo methods. The oximes commonly used for the treatment of acute poisonings with highly toxic organophosphates appeared to be almost ineffective (HI-6, pralidoxime, methoxime) or just slightly effective (obidoxime) against tabun. On the other hand, trimedoxime seemed to be a significantly more efficacious reactivator than the others in the case of tabun poisonings. In vitro, the concentration of trimedoxime corresponding to 1.0 mmol/l was able to reach 50% reactivation of tabun-inhibited brain acetylcholinesterase. Higher reactivating potency of trimedoxime in comparison with the other commonly used oximes was demonstrated by in vivo method, too. In addition, other structural analogues of trimedoxime were found to be efficacious in counteracting tabun-induced acetylcholinesterase inhibition although not as efficacious as trimedoxime itself. Some effective acetylcholinesterase reactivators were characterised by dissociation constant of enzyme-reactivator complex as well as enzyme-inhibitor-reactivator complex and by rate constant of reactivation.

References

Jan 1, 1992·Archives of Toxicology·J G ClementC A Boulet
Oct 1, 1989·Canadian Journal of Physiology and Pharmacology·C G Rousseaux, A K Dua
Mar 1, 1981·Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology·B Bosković
Sep 1, 1994·Journal of Applied Toxicology : JAT·R M Dawson
Dec 12, 2002·Journal of Toxicology. Clinical Toxicology·J Kassa
Jul 1, 1957·Archives of Biochemistry and Biophysics·I B WILSON, F SONDHEIMER
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Jul 8, 1964·Biochimica Et Biophysica Acta·J C LAMBB E HACKLEY
Sep 25, 2003·Bioorganic & Medicinal Chemistry Letters·Kamil KucaJirí Kassa

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Citations

Dec 12, 2007·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Kamil Kuca, Daniel Jun
Jan 6, 2006·International Journal of Toxicology·Lucie BartosovaGabriela Kunesova
Aug 22, 2007·Journal of Toxicology and Environmental Health. Part a·Jiri Kassa, Jana Karasova
Apr 8, 2006·Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia·Kamil KucaVlastimil Dohnal
Dec 30, 2006·Journal of Enzyme Inhibition and Medicinal Chemistry·Martina HrabinovaKamil Kuca
Nov 28, 2012·Expert Opinion on Drug Metabolism & Toxicology·Victor VoicuAndrei Medvedovici
Dec 29, 2007·Drug and Chemical Toxicology·Daniel JunJan Marek
May 16, 2007·Clinical Toxicology : the Official Journal of the American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists·Kamil KucaMartina Hrabinova
Nov 1, 2008·Environmental Toxicology and Pharmacology·Sarka VeselaDaniel Jun
May 1, 2008·Environmental Toxicology and Pharmacology·Sarka VeselaDaniel Jun
May 29, 2009·Basic & Clinical Pharmacology & Toxicology·Kamil KucaMartina Hrabinova
Apr 21, 2006·Basic & Clinical Pharmacology & Toxicology·Kamil KucaVeronika Opletalova
Jun 20, 2007·Basic & Clinical Pharmacology & Toxicology·Kamil KucaLucie Musilova
Sep 26, 2008·Basic & Clinical Pharmacology & Toxicology·Jaroslav PejchalJiri Kassa
Jun 19, 2012·Basic & Clinical Pharmacology & Toxicology·Thiago Henrique LugokenskiFélix Alexandre Antunes Soares
Sep 19, 2009·Toxicology·Elisabet ArturssonFredrik Ekström
Sep 15, 2006·Toxicology Letters·Koichi SakuradaTakehiko Takatori
Aug 27, 2005·Journal of Enzyme Inhibition and Medicinal Chemistry·K KucaJ Kassa
Oct 11, 2011·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Michael D CostaRicardo Brandão

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