In vitro reactivation potency of acetylcholinesterase reactivators--K074 and K075--to reactivate tabun-inhibited human brain cholinesterases

Neurotox Res. 2007 Feb;11(2):101-6. doi: 10.1007/BF03033389.

Abstract

In this work, two oximes for the treatment of tabun-inhibited acetylcholinesterase (AChE; EC 3.1.1.7), K074 (1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide) and K075 ((E)-1,4-bis(4-hydroxyiminomethylpyridinium)but-2-en dibromide), were tested in vitro as reactivators of AChE. Comparison was made with currently used AChE reactivators (pralidoxime, HI-6, methoxime and obidoxime). Human brain homogenate was taken as an appropriate source of the cholinesterases. As resulted, oxime K074 appears to be the most potent reactivator of tabun-inhibited AChE, with reactivation potency comparable to that of obidoxime. A second AChE reactivator, K075, does not attain as great a reactivation potency as K074, although its maximal reactivation (17%) was achieved at relevant concentrations for humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholinesterase / metabolism*
  • Butanes / chemistry
  • Butanes / pharmacology*
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / enzymology*
  • Cholinesterase Inhibitors / toxicity*
  • Cholinesterase Reactivators / chemistry
  • Cholinesterase Reactivators / pharmacology*
  • Enzyme Activation / drug effects
  • Humans
  • In Vitro Techniques
  • Obidoxime Chloride / chemistry
  • Obidoxime Chloride / pharmacology
  • Organophosphates / toxicity*
  • Oximes / chemistry
  • Oximes / pharmacology*
  • Pralidoxime Compounds / chemistry
  • Pralidoxime Compounds / pharmacology
  • Pyridinium Compounds / chemistry
  • Pyridinium Compounds / pharmacology*

Substances

  • 1,4-bis(4-hydroxyiminomethylpyridinium)butane dibromide
  • Butanes
  • Cholinesterase Inhibitors
  • Cholinesterase Reactivators
  • K075 compound
  • Organophosphates
  • Oximes
  • Pralidoxime Compounds
  • Pyridinium Compounds
  • Obidoxime Chloride
  • N,N'-monomethylenebis(pyridiniumaldoxime)
  • Acetylcholinesterase
  • asoxime chloride
  • pralidoxime
  • tabun