In vitro identification of novel acetylcholinesterase reactivators

Abstract

Organophosphate compounds exert toxicity primarily by virtue of acetylcholinesterase (AChE) inactivation at the nerve synapses and neuromuscular junction, leading to accumulation of acetylcholine (ACh). Therefore, treatment of organophosphate poisonings generally relies upon AChE reactivators, anticholinergic drugs, and anticonvulsants. Although there are many structurally different AChE reactivators, only five of them are used clinically. Unfortunately, there is not a single compound that can reactivate inhibited AChE against all nerve agents, or a so-called broad spectrum reactivator. Due to this limitation, the quest for new derivatives continues. For newly synthesized derivatives, in vitro and in vivo evaluation of their reactivation efficacy is of the utmost importance in AChE reactivators’ development. This review article presents literature on the most promising novel AChE reactivators. Furthermore, in vitro and in vivo techniques used for their evaluation are also discussed.

Keywords::

• Acetylcholinesterase
• nerve agents
• organophosphorus inhibitors
• oxime
• reactivator

Acknowledgment

This work was supported by the project of the Czech Grant Agency - No. 305/07/P162.

Declaration of interest: