Citation

Ramalho TC, de Castro AA, Leal DHS, Teixeira JP, de Cunha EFF, Kuca K. Curr. Med. Chem. 2022; ePub(ePub): ePub.

Copyright

(Copyright © 2022, Bentham Science Publishers)

DOI

10.2174/0929867330999221014104610

PMID

36239718

Abstract

INTRODUCTION: Organophosphorus compounds (OP) make up an important class of inhibitors, mostly employed as pesticides, even as chemical weapons. These toxic substances act through the inhibition of the acetylcholinesterase (AChE) enzyme, which results in elevated synaptic acetylcholine (ACh) levels, leading to serious adverse effects under the cholinergic syndrome. Many reactivators have been developed to combat the toxic effects of these AChE inhibitors. In this line, the oximes highlight because of their good reactivating power of cholinesterase enzymes. To date, there are not universal antidotes able to reactivate AChE inhibited by any OP agent. AREAS COVERED: This review summarizes the intoxication process by neurotoxic OP agents, along with the development of reactivators capable of reversing their effects, approaching aspects like therapeutic and toxicological profile of these antidotes. EXPERT OPINION: Computational methods and conscious in vitro studies, capable of significantly predicting the toxicological profile of these drug candidates, might support the process of development of these reactivators before entering in vivo studies in animals, and then clinical trials. These approaches can assist in the design of safer and more effective molecules, reducing related cost and time for the process.

Language: en

Keywords

acetylcholinesterase; computational methods; drug development.; military toxicology; organophosphorus compounds; reactivators