Antidotes in Anticholinesterase Poisoning

Abstract

CERTAIN alkyl phosphates, including a number of widely used insecticides, are toxic to animals, because they irreversibly inhibit acetylcholinesterase¹. Acetylcholinesterase (AChE) is reputed to possess an anionic site, which promotes the catalytic activity by binding and orienting substrates containing a cationic group, and an esteratic site where the hydrolytic process takes place. The interaction between alkyl phosphates and AChE yields phosphorylated AChE which is devoid of esterase activity. The inhibited enzyme can be reactivated by nucleophilic substances which displace the phosphoryl group from the enzyme. The high reactivating potency of pyridine-2-aldoxime methiodide (2–PAM) was first reported by Childs et al.² and Wilson et al.³. The latter authors⁴ attributed the outstanding activity of 2-PAM to binding of its quaternary ammonium group to the anionic site of phosphorylated AChE, and to a suitable orientation of the reactive oximino group for displacement of the phosphoryl group from the esteratic site.