Kinetic Analysis of Oxime Interactions with Acetylcholinesterase as a Basis for the Evaluation of Oxime Efficacy in Organophosphate Poisoning

F.      Worek; P.      Eyer; N.      Aurbek; H.      Thiermann

Abstract

In the past decades a vast number of oximes have been synthesised in order to identify effective compounds for the reactivation of organophosphorus compound (OP)-inhibited acetylcholinesterase (AChE). Up to now, oxime efficacy has been tested primarily in animal experiments. However, the accretive evidence of substantial species differences regarding kinetic properties of human and animal AChE led to an increasing number of in vitro kinetic studies quantifying the reactivating potency of oximes. These data were shown to provide a basis for the selection of effective oximes and for defining adequate oxime doses in human OP poisoning. This review will discuss experimental and theoretical models for the in vitro assessment of oxime efficacy and will give an overview of the present status in the evaluation of oximes as antidotes against OP poisoning.

Keywords: Oxime, organophosphate, acetylcholinesterase, in vitro study