Guanitoxin

Guanitoxin
Names
IUPAC name
(5S)-5-[(Dimethylamino)methyl]-1-{[hydroxy(methoxy)phosphoryl]oxy}-4,5-dihydro-1H-imidazol-2-amine
Identifiers
CAS Number
3D model (JSmol)
ChemSpider
KEGG
PubChem CID
UNII
InChI
  • InChI=1S/C7H17N4O4P/c1-10(2)5-6-4-9-7(8)11(6)15-16(12,13)14-3/h6H,4-5H2,1-3H3,(H2,8,9)(H,12,13)/t6-/m1/s1
    Key: FYXHGVMFJYHPFX-ZCFIWIBFSA-N
SMILES
  • CN(C)C[C@H]1CN=C(N1OP(=O)(O)OC)N
Properties
Chemical formula
 C7H17N4O4P
Molar mass 252.211 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Guanitoxin (GNT), formerly known as anatoxin-a(S) "Salivary"[lower-alpha 1],[1] is a naturally occurring cyanotoxin commonly isolated from cyanobacteria (specifically of the genus Anabaena) and causes excess salivation in mammals via inhibition of acetylcholinesterase. 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.[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. Furthemore, air evaporation of guanitoxin resulted in significant hydrolysis to (5S)-5-[(dimethylamino)methyl]-2-imino-1-imidazolidinol.[2]

Scheme for guanitoxin degradation. Major microspecies at pH 7.4 are shown.

See also

  • Anatoxin-a – a cyanotoxin that shares some clinical exposure signs, and also relates to the same cyanobacteria genera, but with a different chemical structure and toxic mechanism of action
  • Paraoxon – A synthetic pesticide with an analogous mechanism of action

References

  1. ↑ Fiore, Marli Fátima; de Lima, Stella Thomaz; Carmichael, Wayne W.; McKinnie, Shaun M.K.; Chekan, Jonathan R.; Moore, Bradley S. (2020). "Guanitoxin, re-naming a cyanobacterial organophosphate toxin". Harmful Algae. Elsevier BV. 92: 101737. doi:10.1016/j.hal.2019.101737. ISSN 1568-9883. PMID 32113603.
  2. 1 2 Matsunaga, Shigeki; Moore, Richard E.; Niemczura, Walter P.; Carmichael, Wayne W. (1989). "Anatoxin-a(s), a potent anticholinesterase from Anabaena flos-aquae". Journal of the American Chemical Society. American Chemical Society (ACS). 111 (20): 8021–8023. doi:10.1021/ja00202a057. ISSN 0002-7863.
  3. ↑ Hyde, E. G.; Carmichael, W. W. (1991). "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. doi:10.1002/jbt.2570060305. PMID 1770503.
  4. ↑ Mahmood, Nik A.; Carmichael, Wayne W. (1986). "The pharmacology of anatoxin-a(s), a neurotoxin produced by the freshwater cyanobacterium Anabaena flos-aquae NRC 525-17". Toxicon. Elsevier BV. 24 (5): 425–434. doi:10.1016/0041-0101(86)90074-7. ISSN 0041-0101. PMID 3087030.
  5. ↑ Fernandes, Kelly; Ferraz, Humberto; Vereau, Fanny; Pinto, Ernani (2020-11-19). "Availability of Guanitoxin in Water Samples Containing Sphaerospermopsis torques-reginae Cells Submitted to Dissolution Tests". Pharmaceuticals. MDPI AG. 13 (11): 402. doi:10.3390/ph13110402. ISSN 1424-8247. PMC 7699232. PMID 33227987.
  1. ↑ (The "(S)" its name stands for 'salivary' indicating its manner of affliction to distinguish it from a toxin having otherwise the same conventional name. cf. "See also" for aforementioned compound of shared nomenclature.)
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