Saxitoxin

Structural formula
General
Surname	Saxitoxin
other names	STX
Molecular formula	C 10 H 17 N 7 O 4
External identifiers / databases
EC number	632-220-3
ECHA InfoCard	100.160.395
PubChem	37165
Wikidata	Q412694
properties
Molar mass	299.29 g mol −1
solubility	soluble in water and methanol , slightly soluble in ethanol
safety instructions
GHS labeling of hazardous substances danger
H and P phrases	H: 300-310-330
	P: ?
Toxicological data	263 µg kg −1 ( LD 50 , mouse , oral ) ; <2 µg kg −1 ( LD 50 , hamster , inh. ) ;
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

In addition to its related compounds neosaxitoxin (NSTX, NEO, neoSTX) and gonyautoxin (GTX), saxitoxin ( STX ) is an important main representative of neurotoxins (nerve toxins ), which can be accumulated in mussels , mussels or oysters and which, if consumed by humans, result in mussel poisoning (Mytilism) known as paralytic shellfish poisoning (PSP) . Therefore the group of these poisons is also called PSP toxins. The main source of the toxins are dinoflagellates , which are part of the plankton and are consumed by mussels as food. But cyanobacteria , which mainly occur in freshwater, are also able to synthesize saxitoxins. The saxitoxin-producing dinoflagellates include:

Alexandrium catenella ( Gonyaulax catenella )
Alexandrium tamarense excavatum ( Gonyaulax tamarensis )
Pyrodinium bahamense .

These multiply in particular in the warm seasons and can quickly form reddish colored algae carpets in coastal areas (“red tide”).

Saxitoxin can enter the body through inhalation (inhalation), through open wounds, and through food intake. Ingested saxitoxin can lead to fatal respiratory paralysis within minutes to a few hours. Non-lethal doses lead to the following symptoms in humans after a few hours: nausea, vomiting, diarrhea , abdominal pain, muscle pain and headache. Parasitic sensations and visual disturbances occur. The lethal dose varies between 0.5 and 12.4 mg saxitoxin for an adult human (a 50% lethal dose (LD ₅₀ oral) for humans is given as 5.7 µg / kg body weight or more).

Saxitoxin as a chemical warfare agent

Saxitoxin was repeatedly discussed as a chemical warfare agent under the name TZ due to its high toxicity . There are reports that it is believed to be possible to contaminate rifle ammunition with saxitoxin for rapid lethal effects. Saxitoxin is around 1000 times more toxic than the synthetic neurotoxin sarin and, like ricin, is a biological agent. The US American CIA is said to have produced poison capsules with saxitoxin for its agents (e.g. U-2 pilot Gary Powers ) in the 1950s . Saxitoxin is on the war weapons list of the Federal German War Weapons Control Act .

Saxitoxin in medical research

Like the tetrodotoxin , saxitoxin (STX) is an important substance in medical research: It is considered a selective sodium channel blocker that has no influence on the flux of chloride or potassium ions in the cell membrane . The first detailed chemical analysis and synthesis of saxitoxin was carried out by Yoshito Kishi in 1977.

Analytics

After adequate sample preparation, saxitoxin can be used in the various test materials such as HPLC coupling with mass spectrometry . B. plasma or urine can be detected qualitatively and quantitatively. The above-mentioned methods can also be used for examining mussels or fish.

Saxitoxin derivatives, Paralytic Shellfish (Poisoning) Toxins (PSTs, PSP toxins)

PSP toxins describes a group of toxins that are derived from the basic structure of saxitoxin. PSP toxins block voltage-dependent sodium channels in nerve cells . This inhibits the transmission of stimuli in the nerve fibers and the contraction of skeletal muscles , leading to paralysis . Saxitoxin has a comparatively high toxicity and is used as the lead substance for determining the toxicity of the related compounds.

Saxitoxin derivatives

The most important related compounds differ in their chemical residues (R ¹ -R ⁵ , see figure “Saxitoxin derivatives”). The main subdivision of toxins is determined by the chemical residue at position 4 (R ⁴ ). At R ⁴ with carbamoyl group (carbamate): neosaxitoxin , gonyautoxin (I to IV); at R ⁴ with N -sulfo-carbanoyl group (sulfamates): gonyautoxin (V and VI), C-toxins (I to IV); at R ⁴ with a hydroxyl group : decarbamoyl saxitoxin, decarbamoyl gonyautoxin (I to IV), decarbamoyl neosaxitoxin; protonated at R ⁴ ( hydrogen atom , H): deoxydecarbamoyl saxitoxin, deoxydecarbamoyl gonyautoxin (II and III). Furthermore, special toxins of the species Lyngbya wollei (LWTX toxins I to VI) with a methyl group ( esterified ) on R ⁴ and Gymnodinium catenatum (GC toxins I to III) with a phenol residue (esterified) on R ⁴ are mentioned. The chemical radicals R ¹ , R ² , R ³ and R ⁵ differ in different combinations of a hydroxyl group, a hydrogen atom or an organosulfate group.
A saxitoxin derivative that has a higher toxic potency than the saxitoxin itself is e.g. B. the zetekitoxin .

Web links

Saxitoxin in the dinoflagellate species Gonyaulax catenella
PSP in Alaska (English; PDF file; 1.4 MB)
scinexx.de
Spiez Laboratory: Factsheet Saxitoxin (Mytilotoxin; Shellfish Toxine; STX, PSP) (PDF, 213 kB)

Individual evidence

↑ ^a ^b Data sheet at CbInfo ( Memento of the original from October 14, 2007 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. . @1@ 2

↑ There is not yet a harmonized classification for this substance . A labeling of saxitoxin in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on March 13, 2019, is reproduced from a self-classification by the distributor .

^ ^A ^b ^c Lyndon E. Llewellyn: Saxitoxin, a toxic marine natural product that targets a multitude of receptors . In: Natural Product Reports . tape 23 , no. 2 , 2013, p. 200-222 , doi : 10.1039 / B501296C .

↑ JD Hackett, JH Wisecaver, ML Brosnahan, DM Kulis, DM Anderson, D. Bhattacharya, FG Plumley, DL Erdner: Evolution of saxitoxin synthesis in cyanobacteria and dinoflagellates. In: Mol Biol Evol. 30 (1), Jan 2013, pp. 70-78. PMID 22628533 .

↑ JP Parkhill, AD Cembella: Effects of salinity, light and inorganic nitrogen on growth and toxigenicity of the marine dinoflagellate Alexandrium tamarense from northeastern Canada . In: Journal of Plankton Research . tape 21 , no. 5 , 1999, p. 939–955 , doi : 10.1093 / plankt / 21.5.939 .

^ A. Schrader, O. Strubelt, G. Wagner, F. Amelung: Tierische Gifte. In: A. Schrader (ed.): Toxic diseases of the nervous system. Springer-Verlag, Berlin / New York 1992, pp. 229-263, Section D: Saxitoxin-Intoxikation, p. 256.

^ S. Faber: Saxitoxin and the induction of paralytic shellfish poisoning . In: Journal of Young Investigators . tape 23 , no. 1 , 2012, p. 1-7 ( jyi.org ).

↑ J. Patocka, L. Stredav: Brief Review of Natural Nonprotein Neurotoxins. In: Richard Price (Ed.): ASA Newsletter. (Applied Science and Analysis inc.) 02-2 (89), April 23, 2002, pp. 16-23. ISSN 1057-9419 .

^ War Weapons List of the War Weapons Control Act

↑ H. Tanino, T. Nakata, T. Kaneko, Y. Kishi: A stereospecific total synthesis of dl-saxitoxin. In: Journal of the American Chemical Society. 99, 1977, p. 2818, doi : 10.1021 / ja00450a079 .

↑ synarchive.com: Synthesis of Saxitoxin , accessed on August 16, 2017.

↑ ^a ^b K. Harju, ML Rapinoja, MA Avondet, W. Arnold, M. Schär, S. Burrell, W. Luginbühl, P. Vanninen: Optimization of Sample Preparation for the Identification and Quantification of Saxitoxin in Proficiency Test Mussel Sample using Liquid Chromatography-Tandem Mass Spectrometry. In: Toxins. (Basel). 7 (12), Nov 25, 2015, pp. 4868-4880. PMID 26610567

↑ RW Peake, VY Zhang, N. Azcue, CE Hartigan, A. Shkreta, J. Prabhakara, CB Berde, MD Kellogg: Measurement of neosaxitoxin in human plasma using liquid-chromatography tandem mass spectrometry: Proof of concept for a pharmacokinetic application. In: J Chromatogr B Analyt Technol Biomed Life Sci. 1036-1037, Oct 1, 2016, pp. 42-49. PMID 27710889

↑ WA Bragg, SW Lemire, RM Coleman, EI Hamelin, RC Johnson: Detection of human exposure to saxitoxin and neosaxitoxin in urine by online-solid phase extraction-liquid chromatography-tandem mass spectrometry. In: Toxicon. 99, Jun 1, 2015, pp. 118-124. doi: 10.1016 / j.toxicon.2015.03.017 Epub 2015 Mar 27. PMID 25817003

↑ T. Nakatani, M. Shimizu, T. Yamano: The Contents and Composition of Tetrodotoxin and Paralytic Shellfish Poisoning Toxins in Marine Pufferfish Canthigaster rivulata. In: Shokuhin Eiseigaku Zasshi. 57 (2), 2016, pp. 51–56. PMID 27211919 .

↑ ^a ^b Brenton Nicholson, John Papageorgiou, Andrew E. Humpage, Paul Monis, Dennis Steffensen: Determination and Significance of Emerging Algal Toxins (Cyanotoxins) . American Water Works Association, 2007, ISBN 978-1-58321-536-4 , p. 50 ( limited preview in Google book search).

↑ M. Yotsu-Yamashita, YH Kim, SC Dudley Jr, G. Choudhary, A. Pfahnl, Y. Oshima, JW Daly: The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium- channel blocker . In: Proceedings of the National Academy of Sciences . tape 101 , no. 13 , 2013, p. 4346-4351 , doi : 10.1073 / pnas.0400368101 .

[cbwinfo-1] Data sheet at CbInfo ( Memento of the original from October 14, 2007 in the Internet Archive ) Info: The archive link was automatically inserted and not yet checked. Please check the original and archive link according to the instructions and then remove this notice. . @1@ 2

[2] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of saxitoxin in the Classification and Labeling Inventory of the European Chemicals Agency (ECHA), which was retrieved on March 13, 2019, is reproduced from a self-classification by the distributor .

[CLlewellyn-3] A ^b ^c Lyndon E. Llewellyn: Saxitoxin, a toxic marine natural product that targets a multitude of receptors . In: Natural Product Reports . tape 23 , no. 2 , 2013, p. 200-222 , doi : 10.1039 / B501296C .

[4] JD Hackett, JH Wisecaver, ML Brosnahan, DM Kulis, DM Anderson, D. Bhattacharya, FG Plumley, DL Erdner: Evolution of saxitoxin synthesis in cyanobacteria and dinoflagellates. In: Mol Biol Evol. 30 (1), Jan 2013, pp. 70-78. PMID 22628533 .

[5] JP Parkhill, AD Cembella: Effects of salinity, light and inorganic nitrogen on growth and toxigenicity of the marine dinoflagellate Alexandrium tamarense from northeastern Canada . In: Journal of Plankton Research . tape 21 , no. 5 , 1999, p. 939–955 , doi : 10.1093 / plankt / 21.5.939 .

[6] A. Schrader, O. Strubelt, G. Wagner, F. Amelung: Tierische Gifte. In: A. Schrader (ed.): Toxic diseases of the nervous system. Springer-Verlag, Berlin / New York 1992, pp. 229-263, Section D: Saxitoxin-Intoxikation, p. 256.

[7] S. Faber: Saxitoxin and the induction of paralytic shellfish poisoning . In: Journal of Young Investigators . tape 23 , no. 1 , 2012, p. 1-7 ( jyi.org ).

[8] J. Patocka, L. Stredav: Brief Review of Natural Nonprotein Neurotoxins. In: Richard Price (Ed.): ASA Newsletter. (Applied Science and Analysis inc.) 02-2 (89), April 23, 2002, pp. 16-23. ISSN 1057-9419 .

[9] War Weapons List of the War Weapons Control Act

[DOI10.1021/ja00450a079-10] H. Tanino, T. Nakata, T. Kaneko, Y. Kishi: A stereospecific total synthesis of dl-saxitoxin. In: Journal of the American Chemical Society. 99, 1977, p. 2818, doi : 10.1021 / ja00450a079 .

[11] synarchive.com: Synthesis of Saxitoxin , accessed on August 16, 2017.

[K._Harju,_M._L_2015-12] K. Harju, ML Rapinoja, MA Avondet, W. Arnold, M. Schär, S. Burrell, W. Luginbühl, P. Vanninen: Optimization of Sample Preparation for the Identification and Quantification of Saxitoxin in Proficiency Test Mussel Sample using Liquid Chromatography-Tandem Mass Spectrometry. In: Toxins. (Basel). 7 (12), Nov 25, 2015, pp. 4868-4880. PMID 26610567

[13] RW Peake, VY Zhang, N. Azcue, CE Hartigan, A. Shkreta, J. Prabhakara, CB Berde, MD Kellogg: Measurement of neosaxitoxin in human plasma using liquid-chromatography tandem mass spectrometry: Proof of concept for a pharmacokinetic application. In: J Chromatogr B Analyt Technol Biomed Life Sci. 1036-1037, Oct 1, 2016, pp. 42-49. PMID 27710889

[14] WA Bragg, SW Lemire, RM Coleman, EI Hamelin, RC Johnson: Detection of human exposure to saxitoxin and neosaxitoxin in urine by online-solid phase extraction-liquid chromatography-tandem mass spectrometry. In: Toxicon. 99, Jun 1, 2015, pp. 118-124. doi: 10.1016 / j.toxicon.2015.03.017 Epub 2015 Mar 27. PMID 25817003

[15] T. Nakatani, M. Shimizu, T. Yamano: The Contents and Composition of Tetrodotoxin and Paralytic Shellfish Poisoning Toxins in Marine Pufferfish Canthigaster rivulata. In: Shokuhin Eiseigaku Zasshi. 57 (2), 2016, pp. 51–56. PMID 27211919 .

[Brenton-16] Brenton Nicholson, John Papageorgiou, Andrew E. Humpage, Paul Monis, Dennis Steffensen: Determination and Significance of Emerging Algal Toxins (Cyanotoxins) . American Water Works Association, 2007, ISBN 978-1-58321-536-4 , p. 50 ( limited preview in Google book search).

[17] M. Yotsu-Yamashita, YH Kim, SC Dudley Jr, G. Choudhary, A. Pfahnl, Y. Oshima, JW Daly: The structure of zetekitoxin AB, a saxitoxin analog from the Panamanian golden frog Atelopus zeteki: a potent sodium- channel blocker . In: Proceedings of the National Academy of Sciences . tape 101 , no. 13 , 2013, p. 4346-4351 , doi : 10.1073 / pnas.0400368101 .