Pralidoxime: a review of its synthesis and antidotal properties against warfare nerve agents

Abstract

Acetylcholinesterase (AChE) is an enzyme in the central and peripheral nervous systems that has been studied in fields of research such as that for Alzheimer’s and Parkinson’s diseases. AChE inhibitors may be either natural or synthetic, which is the case of the organophosphorus compounds, developed as chemical weapons or pesticides, the latter of which is less toxic. The inhibition of organophosphorus is irreversible and is carried out by binding the phosphorus atom to the hydroxyl group of the serine residue within the active site of the AChE, thus preventing AChE from fulfilling its physiological task in cholinergic transmissions, possibly leading to respiratory failure and death. Due to their strong nucleophilic character, AChE reactivators can cleave the bond between the serine residue and the adduct, reestablishing enzymatic activity. This study describes the biological properties and the diverse synthetic methods for pralidoxime, the first AChE reactivator clinically applied.