Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary", is a naturally occurring

cyanotoxin Cyanotoxins are toxins produced by cyanobacteria (also known as blue-green algae). Cyanobacteria are found almost everywhere, but particularly in lakes and in the ocean where, under high concentration of phosphorus conditions, they reproduce exp ...

commonly isolated from cyanobacteria (specifically of the genus ''Anabaena'') and causes excess salivation in mammals via inhibition of

acetylcholinesterase Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acety ...

. Guanitoxin was first structurally characterized in 1989, and consists of a cyclic ''N''-hydroxyguanine

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

with a phosphate ester moiety.

Toxicity and treatment

The main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

in the parasympathetic and peripheral nervous systems; inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation. The clinical signs of high level guanitoxin exposure consists mainly of excessive salivation, lacrimation, chromodacryorrhea (in rats), urinary incontinence, muscular weakness, muscle twitching, convulsion, including opisthotonus, and respiratory distress and/or failure. Treatment of afflicted case by

atropine Atropine is a tropane alkaloid and anticholinergic medication used to treat certain types of nerve agent and pesticide poisonings as well as some types of slow heart rate, and to decrease saliva production during surgery. It is typically giv ...

has attested to suppress the muscarinic mediated toxicity; which prevents the namesake salivation that similarly reacts to prevent the toxin's other poisoning symptoms which include lacrimation, urinary incontinence and defecation. Atropine will not, however, counter another mechanism of the compounds toxicity as it also mediates a nicotinic adverse toxicity affecting muscle tremors, fasciculation, convulsions and respiratory failure.

Stability and degradation

Guanitoxin is generally labile. It decomposes rapidly in basic solutions, but is relatively stable in neutral or acidic solutions (pH 3-5). When stored at -20˚C, it slowly undergoes hydrolysis giving (5S)-5- dimethylamino)methyl2-imino-1-imidazolidinol and monomethyl-phosphate, and more slowly, formation of (S)-1-(2-iminoimidazolidin-4-yl)-N,N-dimethylmethanamine. Furthemore, air evaporation of guanitoxin resulted in significant hydrolysis to (5S)-5- dimethylamino)methyl2-imino-1-imidazolidinol. Scheme for Guanitoxin degradation

References

{{Acetylcholine metabolism and transport modulators Acetylcholinesterase inhibitors Neurotoxins Guanidine alkaloids Organophosphates Methyl esters Cyanotoxins Nitrogen heterocycles Dimethylamino compounds Bacterial alkaloids

Toxicity and treatment

Stability and degradation

See also

References