Anatoxin-a(s): Natural Organophosphorus Anticholinesterase Agent

Anatoxin-a(s) is a guanidinemethyl phosphate ester isolated from the freshwater cyanobacterium (bluegreen algae) Anabaena flos-aquae strain NRC 525–17. Previous work has shown anatoxin-a(s) to be a potent irreversible inhibitor of electric eel acetylcholinesterase (AChE, EC 3.1.1.7). Anatoxin-a(s) has been shown to be an active site-directed inhibitor of AChE, which is resistant to reactivation by oximes because of the enzyme-oxime adduct formation. In vivo pretreatment with physostigmine and high concentrations of pyridine 2-aldoxime methochloride (2-PAM) were the only effective antagonists against a lethal dose of anatoxin-a(s). Anatoxin-a(s) is very toxic and it is produced by cyanobacteria during its blooms. Purified toxin has an LD50 (i.p) of approximately 20-50 μg/kg body weight in mice. Toxicoses associated with cholinesterase-inhibiting anatoxin-a(s) have been observed in humans, animals, birds and fish. Anatoxina(s) induces clinical signs of hypercholinergic preponderance, such as salivation, lacrimation, urinary incontinence, defecation, convulsion, fasciculation, and respiratory arrest.