Guanitoxin Explained

Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary",[1] is a naturally occurring cyanotoxin commonly isolated from cyanobacteria (specifically of the genus Anabaena). It is a potent covalent acetylcholinesterase inhibitor, and thus a potent rapid acting neurotoxin which in cases of severe exposure can lead to death. Guanitoxin was first structurally characterized in 1989, and consists of a cyclic N-hydroxyguanine organophosphate with a phosphate ester moiety.[2]

Toxicity and treatment

The main mechanism of action for guanitoxin is by irreversibly inhibiting the active site of acetylcholinesterase leading to excess acetylcholine in the parasympathetic and peripheral nervous systems; inducing poisoning via nicotinic and muscarinic cholinergic receptor stimulation.[3] 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, and death.[4] [5]

Treatment of afflicted case by atropine 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)methyl]-2-imino-1-imidazolidinol and monomethyl-phosphate, and more slowly, formation of (S)-1-(2-iminoimidazolidin-4-yl)-N,N-dimethylmethanamine. Furthermore, air evaporation of guanitoxin solutions resulted in significant hydrolysis to (5S)-5-[(dimethylamino)methyl]-2-imino-1-imidazolidinol.

See also

Notes and References

  1. Fiore . Marli Fátima . de Lima . Stella Thomaz . Carmichael . Wayne W. . McKinnie . Shaun M.K. . Chekan . Jonathan R. . Moore . Bradley S. . Guanitoxin, re-naming a cyanobacterial organophosphate toxin . Harmful Algae . Elsevier BV . 92 . 2020 . 1568-9883 . 10.1016/j.hal.2019.101737 . 101737. 32113603 . 211725815 .
  2. Matsunaga . Shigeki . Moore . Richard E. . Niemczura . Walter P. . Carmichael . Wayne W. . Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae . Journal of the American Chemical Society . American Chemical Society (ACS) . 111 . 20 . 1989 . 0002-7863 . 10.1021/ja00202a057 . 8021–8023.
  3. 1770503. 1991. Hyde. E. G.. Anatoxin-a(s), a naturally occurring organophosphate, is an irreversible active site-directed inhibitor of acetylcholinesterase (EC 3.1.1.7). Journal of Biochemical Toxicology. 6. 3. 195–201. Carmichael. W. W.. 10.1002/jbt.2570060305.
  4. Mahmood . Nik A. . Carmichael . Wayne W. . The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17 . Toxicon . Elsevier BV . 24 . 5 . 1986 . 0041-0101 . 10.1016/0041-0101(86)90074-7 . 425–434. 3087030 .
  5. Fernandes . Kelly . Ferraz . Humberto . Vereau . Fanny . Pinto . Ernani . Availability of Guanitoxin in Water Samples Containing Sphaerospermopsis torques-reginae Cells Submitted to Dissolution Tests . Pharmaceuticals . MDPI AG . 13 . 11 . 2020-11-19 . 1424-8247 . 10.3390/ph13110402 . 402. 33227987 . 7699232 . free .