Anatoxin‐A(S), a naturally occurring organophosphate, is an irreversible active site‐directed inhibitor of acetylcholinesterase (EC 3.1.1.7)

Publisher Website
Google Scholar
Abstract
Anatoxin‐a(s) is a guanidine methyl phosphate ester (unprotonated molecular ion equals 252 daltons) isolated from the freshwater cyanobac‐terium (blue‐green alga) Anabaena flos‐aquae strain NRC 525–17. Previous work has shown anatoxin‐a(s) to be a potent irreversible inhibitor of electric eel ace‐tylcholinesterase (EC 3.1.1.7, AChE). In the present study the interaction of anatoxin‐a(s) with AChE was investigated by protection studies and since similarities have been noted between anatoxin‐a(s) and the synthetic organophosphate anticholinesterases, the ability of reactivators to reactivate the inhibited enzyme was investigated. Treatments directed toward eliminating poisoning symptoms and in vivo protection from anatoxin‐a(s) poisonings were investigated using oxime reactivators and atropine or pretreatment with a carbamate and atropine. Anatoxin‐a(s) was shown to be an active site‐directed inhibitor of acetyl‐cholinesterase which is resistant to oxime reactivation due to the structure of its enzyme adduct. In vivo pretreatment with physostigmine and high concentrations of 2‐PAM were the only effective antagonists against a lethal dose of anatoxin‐a(s).