Talk:Tetrodotoxin

Untitled
Note: This article contains some material derived from the public domain article "Tetrodotoxin", from the Bad Bug Book, available at http://vm.cfsan.fda.gov/~mow/chap39.html  — Preceding unsigned comment added by The Anome (talk • contribs) 17:09, 21 June 2004 (UTC)

Synthetic version?
Would it be possible to make a synthetic version of this compound? Does anyone know how much it would cost? --Cyberman 01:53, 12 July 2005 (UTC)


 * To date, there are three total syntheses of TTX. Each took several people several years to develop.  In the end, they had a few milligrams of pure TTX.  I imagine following these routes would cost you between $500K and $1000K per gram of material.  Good luck. ~K 03:07, 12 July 2005 (UTC)


 * I think a fish farm would be better. Thanks. Cyberman


 * I thought the whole idea of total synthesis was that since the precursors are very low cost (simple sugars and petrochemicals) the processes were actually quite cheap. Industrial production of many more complex chemicals makes pharmaceuticals for pennies a pill. 70.70.136.240 01:45, 18 August 2007 (UTC)


 * The starting materials may be cheap, but total synthesis of molecules of this complexity require many steps, so that the total cost is quite expensive. Perhaps the synthesis could be optimized to lower the costs, but even then it would be very difficult to compete with material isolated from natural sources or produced through fermination. Boghog2 22:00, 6 November 2007 (UTC)

Toxicity
Does anyone have an LD50 for tetrodoxin, in rats or rabbits or anything? another page claims it is the most powerful neurotoxin, it would be nice for comparisons sake, as I have heard saxitoxin and some of the chemical nerve agents claimed too. — Preceding unsigned comment added by 70.70.136.240 (talk) 01:45, 18 August 2007 (UTC)

Zombie Potions

 * From the text
 * Only a few cases have been reported in the United States, and outbreaks in countries outside the Indo-Pacific area are rare, except in Haiti, where Tetrodotoxin plays a key role in the creation of so called zombie poisons.

Is there a scientific reference that confirms this as more than urban legend? — Preceding unsigned comment added by 128.9.208.128 (talk) 20:41, 14 August 2006 (UTC)


 * You mean like reference #9 in the article? Unfortunately there is no PubMed abstract and the pdf costs money, but the title certainly suggests that there is at least some documented evidence. Cheers Boghog2 21:55, 6 November 2007 (UTC)


 * The pdf contains a so-called "Letter to the Editor". While the title might suggest that there is documented evidence for a link between TTX and the "zombie"-phenomenon, the contrary is the case. The author (Anderson, Mass. Gen. Hosp., Boston) explains very clearly that there is no evidence, and no proof for the theses set up by Davis. In fact, scientific rigor and ethics of the latter is questioned very strongly. Furthermore it seems, that Davis never tried to set the record right by publishing evidence for his claims. — Preceding unsigned comment added by 155.91.64.10 (talk) 14:42, 8 November 2007 (UTC)
 * Thanks for providing a summary of the "Letter to the Editor". Having access to the letter, you are in much better position than I to correct the "Zombie Potions" section of this article.  The simplest solution is to delete the section entirely.  Perhaps a better solution would be to summarize the available evidence which refutes the hypothesis.  What do you think? Boghog2 19:21, 8 November 2007 (UTC)

"The Serpent and the Rainbow" by Wade Davis would provide the source. This is a non-fiction account of a Harvard scientist sent to Haiti to identify the Zombie toxin, which was indeed a mix of tetrodotoxin with other ingredients. Foolio93 23:01, 15 January 2007 (UTC)


 * Anecdotal. 129.174.111.225 18:31, 18 September 2007 (UTC)


 * Reading the literature kindly provided to us by the author of this article it seems that in the samples collected to prove the presence of Tetrodotoxin actually did not contain any of it - a fact which the author Davis somewhat neglects since it doesn't seem to fit his theory. —Preceding unsigned comment added by 155.91.64.10 (talk) 16:02, 6 November 2007 (UTC)

Role of TTX-r neurones in pain
This article only says that TTX-r channels are found in the heart - they are also found in pain pathways a lot - I dont know enough to update this, but feel that someone sould Ged3000 14:28, 17 December 2006 (UTC)

Film
Wes Cravens 'the serpent and the rainbow' film features this compound — Preceding unsigned comment added by 71.145.195.14 (talk) 20:59, 4 January 2007 (UTC)

Physiology

 * From the text
 * The toxin blocks the fast Na+ current in human myocytes (the contractile cells of the heart), thereby inhibiting their contraction. By contrast, the sodium channels in pacemaker cells of the heart are of the slow variety, so action potentials in the cardiac nodes are not inhibited by the compound. The poisoned individual therefore dies not because the electrical activity of the heart is compromised, but because the myocytes are effectively paralyzed.

Can this be referenced? I was of the belief that TTX shows low affinity for cardiac mycocyte Na channels (1000x lower than for skeletal or neuronal channels). Jwebb1286 16:42, 25 February 2007 (UTC)
 * Agreed; I don't think that the description is right, and as it hasn't been referenced in the last 8 years, I've deleted it.Klbrain (talk) 11:56, 23 August 2015 (UTC)

Suggestion for Antidote Research
the c=N-H might be subject to reaction with the sulfhydryl group of acetylcysteine, I do not know, if it did massive doses would be required, but acetylcystine is non-toxic and used in acetaminophen poisoning. This is just a research suggestion from a retired pharmacist.

71.114.183.105 (talk) 06:50, 17 January 2008 (UTC)

Hard data on fugu poisoning in Japan
Here's some hard data on fugu poisonings and deaths in Japan in the last decade. It's in Japanese, but the first table shows incidents throughout the country (columns: year, # of incidents, # of people poisoned, # of people dead), while the second shows cases in Tokyo alone (columns: year, # of people who ate the fish, # of people poisoned, # of people dead, type of fish, cause of poisoning). To summarize, an average of 40-odd cases throughout the country, with 50-odd people poisoned and 0-6 deaths per year -- way less than the common claims of "hundreds of people dead every year". Jpatokal (talk) 04:10, 21 April 2008 (UTC)

Oregon death?
The line "at least one report of a fatal episode in Oregon when an individual swallowed a Rough-skinned Newt" doesn't have a reference.

Chrishavel (talk) 15:46, 10 August 2009 (UTC) Chris Havel

Tetrodotoxine used as a rape drug
I believe I was repeatedly drugged with a tetrodotoxin as a child by my step-grandfather who was a child abusing restaurant owner in New York City. He purchased the drug from a Haitian man who claimed to be the descendant of royalty in Haiti before his family was overthrown. I was basically paralyzed with mental awareness and physical sensation but no motor skills. After recovering from paralysis, I attempted to call the police but was locked in a room for 3 days in a near-death state with no water or food and then nursed back to health. With repeated poisoning, I suffered brain and nerve damage with loss of verbal skills and involuntary facial twitching. I certainly looked and felt like a zombie. Peers named called me "vegetable". The more symptoms I displayed, the more I was locked up. I suffered amnesia and recovered memories of the abuse 30+ years after the fact. I am sharing my story to let you know that the drug has been used more extensively than people realize. — Preceding unsigned comment added by 69.229.62.79 (talk) 22:47, 29 August 2009 (UTC)


 * This must have been terrible! I would that have thought that tetrodotoxin would paralyze the muscles involved in breathing, so to receive a dose high enough to cause a whole-body paralysis would probably have caused death. I wonder if some other drug/toxin could have been involved?Klbrain (talk) 12:00, 23 August 2015 (UTC)

lol
I was looking this article up while studying about sodium and look what I found:

"The amount needed to reach a lethal dose by injection is much smaller, 8 μg per kg,[20] or a little over one-half milligram (0.00002 oz) per person. Or 4 gallons (15.1416472 litres)of pufferfish poison to knock out Rosie O' Donnel." what's crazy is that has been there for over a year Rob Cypher (talk) 02:17, 7 October 2009 (UTC)

Not always endosymbiotic
I'm not quite sure how to work this in, but Newts are thought to produce TTX without the aid of bacteria (http://dx.doi.org/10.1016/j.toxicon.2004.05.019). Some fish seem to do this as well, though the article is correct in that bacteria are the source of TTX for most animals. This becomes important regarding Newts in captivity (e.g. pets), as they remain quite poisonous (http://www.caudata.org/forum/f1173-advanced-newt-salamander-topics/f30-species-genus-family-discussions/f40-north-american-newts-notophthalmus-taricha/58391-effect-ttx-garter-snakes.html#post171028) in contrast to most fish which become harmless without the wild bacteria. —Preceding unsigned comment added by 74.132.149.73 (talk) 00:33, 29 October 2010 (UTC)


 * There is also work published that has shown production of ttx by bacteria isolated from newts. The paper by Lehman, Brodie & Brodie failed to cite that previous study, so evidently they were unaware of that work or chose to ignore it in their Discussion. Lehman et al. did find bacteria in the gut of newts. Couldn't those bacteria be producing TTX? Like puffers, I would guess that newts raised axenically would also be non-tetrodotoxic. There is no evidence that newts produce ttx.Sushilover2000 (talk) 20:37, 29 October 2010 (UTC)


 * It seems that this is a controversial area and there isn't any direct evidence for either position (e.g. a TTX gene or known TTX-producing bacteria). As newts are fairly long-lived creatures, there seems to be no evaluation of their toxicity when raised axenically, though many species do retain or increase toxicity in captivity.  Interestingly, there are significant enough differences between marine organisms and salamanders in regards to toxicity to make it unlikely that they produce TTX in the same manner (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2857372/). 74.132.145.60 (talk) 23:03, 16 December 2010 (UTC)

What is the dominant form of Na+ channel in the heart; TTXr or TTXs?
My professor pointed out this recent (2010) review which suggests, in passing, that the predominant form of voltage-gated Na+ channel in the heart is TTXr, not TTXs as suggested in the article. This would certainly make questionable the actions of TTX on the heart. She felt the truth may somewhere between the extremes; does anyone have more explicit references on the topic?

Structure and function of splice variants of the cardiac voltage-gated sodium channel Na(v)1.5. [Review] [72 refs] Schroeter A. Walzik S. Blechschmidt S. Haufe V. Benndorf K. Zimmer T. Journal of Molecular & Cellular Cardiology. 49(1):16-24, 2010 Jul. [Journal Article. Review] UI: 20398673

AB Voltage-gated sodium channels mediate the rapid upstroke of the action potential in excitable tissues. The tetrodotoxin (TTX) resistant isoform Na(v)1.5, encoded by the SCN5A gene, is the predominant isoform in the heart. This channel plays a key role for excitability of atrial and ventricular cardiomyocytes and for rapid impulse propagation through the specific conduction system. During recent years, strong evidence has been accumulated in support of the expression of several Na(v)1.5 splice variants in the heart, and in various other tissues and cell lines including brain, dorsal root ganglia, breast cancer cells and neuronal stem cell lines. This review summarizes our knowledge on the structure and putative function of nine Na(v)1.5 splice variants detected so far. Attention will be paid to the distinct biophysical properties of the four functional splice variants, to the pronounced tissue- and species-specific expression, and to the developmental regulation of Na(v)1.5 splicing. The implications of alternative splicing for SCN5A channelopathies, and for a better understanding of genotype-phenotype correlations, are discussed. Copyright 2010 Elsevier Ltd. All rights reserved. [References: 72] —Preceding unsigned comment added by 98.157.151.98 (talk) 21:04, 26 February 2011 (UTC)

Octopodes vs. octapuses
I noticed that in the section "Sources in Nature," the second line uses the term octapodes, whereas the second to last line uses the term octapuses. I'm aware that the former is more correct, but I believe that the latter is more widely accepted. Does anyone know which is preferred on Wikipedia? — Preceding unsigned comment added by 38.104.189.46 (talk) 17:40, 29 June 2011 (UTC)

I standardized this to octopuses, cf. http://en.wikipedia.org/wiki/Plural_form_of_words_ending_in_-us#Octopus. Sushilover2000 (talk) 17:25, 4 July 2011 (UTC)

Symptoms and treatment
The third paragraph largely duplicates the contents of the second one and appears to be an attempt to present the same information in a form that doesn't require a medical degree to comprehend it. Suggest merging whatever contents of the second para is not covered in the third one there and delete the rest as redundant. --illythr (talk) 01:32, 31 July 2011 (UTC)

Maculotoxin citation
Unsure of how to add citations to the article, but if someone wants to add it please do: The 1978 study that showed Maculotoxin to be identical in structure to Tetrodotoxin is as follows: 'SHEUMACK, DD, HOWDEN, MEH, SPENCE, I. and QUINN, RJ., 1978, Maculotoxin - Neurotoxin from Venom Glands of Octopus Hapalochlaena-Maculosa Identified as Tetrodotoxin. Rid A-7931-2008' — Preceding unsigned comment added by 82.26.246.183 (talk) 12:05, 2 March 2012 (UTC)

Western-orientated history
Currently this article states: "The first recorded cases of tetrodotoxin poisoning were from the logs of Captain James Cook from 7 September 1774" With all the ignorance of the intolerable statement that America was "discovered" in 1492. Forget about those who were already there, huh! Asians have been eating this fish for centuries, how on earth can Cook's experience be even remotely considered the "first recorded case"? It might be the first European incidence but it was most likely not the first noted case. But the problem I suppose is how many people actually understand Nihongo or better still actually understand [a cognitive argument]?

An old saying from China states "when you eat the puffer fish you die". Or does the Western-centric nature of this website preclude what the rest of the world says?86.147.58.218 (talk) 18:32, 18 May 2012 (UTC)


 * Agreed. I've added some more historical background, mainly from Chinese primary sources interpreted by an expert Japanese secondary source. I've also corrected 'in the Western literature', because this isn't quite right either (I've inserted a discussion of a publication by an early Dutch physician). So, the James Cook reference can perhaps remain as the first recorded example of Westerners being poisoned (appropriately reworded).Klbrain (talk) 12:07, 23 August 2015 (UTC)

Other Food Poisoning Modes?
I found this page following a link from the page on food poisoning. If the bacteria which cause it do not occur outside of larger living creatures, this is not stated. Is the ambiguity there, or here? In short: can a person 'get it' from eating food that these bacteria have colonized, or does it have to be a food that had the bacteria living in it during it's lifespan? Or is this unknown? Also, there seems to be an implication that this toxin can survive in the open environment. Is this so? Ernest C. Ruger (talk) 16:58, 4 October 2013 (UTC)


 * My understanding is that the toxin is 'concentrated' in some organs in the fish, to such an extent that it becomes toxic. The implication is that the concentration in open environment is usually too low, unless the environment has been deliberately spiked with the toxin, of course.Klbrain (talk) 12:10, 23 August 2015 (UTC)

Mental impairment?
What causes this? Is it:

1. Hypoxia from interference with breathing? 2. Interference with neurons' metabolism? 3. Interferes with brain function by affecting neurotransmitters?

My impression from this article and things I have read elsewhere that if someone recovers there is no lasting damage so what sort of thing causes only temporary impairment?--Jrm2007 (talk) 02:18, 26 June 2014 (UTC)

Tetrodotoxin Resistance in Garter Snakes
Another topic that could be added to this selection is how garter snakes have become adapted to tetrodotoxin and have a resistance against it. Due to its prey (Taricha granulosa-newts) being toxic, it has developed this trait. If the population of garter snakes is in the same area as the newts, then they have a higher tolerance for the toxin. Nguyen.332 (talk) 05:22, 1 October 2014 (UTC)

25 July 2015 edits
In todays editing I did the following:
 * Removed Synthesis as a subheading under Biochemistry (because this is simply an inaccurate reflection of what field this work lies within). Edited to "Chemical synthesis" and raise its heading level.


 * In the ‎"Poisoning" section, Merged redundant toxicity subheadings, one with label, one without. I ALSO DELETED THE 1.5 SENTENCES THAT MADE STATEMENTS ASSUMING QUANTITATIVELY COMPARABLE TOXICITY IN HUMANS, BASED ON CALCULATIONS FROM MOUSE DATA—AS BASELESS SPECULATION.


 * In the ‎"Symptoms and treatment" section, noted repeat paragraphs with significantly redundant symptomology lists, as well as—critically—somewhat differing and therefore internally contradictory onset data, etc. These two sequential paragraphs need to be reconciled, consulting the original or better sources. Missing or poor citations in this section were also noted.


 * In that same section, noted that many sentences that are unclear as to source, because of sparse use of inline citations. Also noted lack of review sources (reliance on primary sources), generally.


 * In the new "Chemical synthesis" section, noted a clear failure to establish discoveries with other than editor OR-selected primary sources, as well as the general datedness of content.

Any questions, discuss here (before reverting, part or all). Thank you. Le Prof. Leprof 7272 (talk) 08:11, 25 July 2015 (UTC)


 * I've been busily working through some of your numerous suggestions for improving this article, including citing recent review articles (in peer-reviewed scientific journals), online drug databases (IUPHAR/BPS), and a Pharmacology textbook or two. There is more to be done, but I think its a start.Klbrain (talk) 00:20, 23 August 2015 (UTC)
 * I've tried to address all of the tagged issues, and added some more bits and pieces (particularly in the history section, from my reading of a good review from the 60s). Given this, I've removed the tags, but don't mind you adding them back if you feel that some things haven't been adequately addressed.Klbrain (talk) 17:38, 23 August 2015 (UTC)

Tag cleanup
Some parts of the article had a massive mess of mostly unnecessary tags. The majority of these were "secondary source needed" -tags, which didn't seem very relevant as the sources provided next to them were sufficient in context. There was also a couple of regular old citation needed -tags right next to a valid citation, as well as some duplicate tags. I left the additional secondary and tertiary sources tag at the top because the majority of the sources in the article are technically primary sources, being scientific journals. I think they're sufficient in the context they're provided, but whatever. -- turdastalk 00:00, 11 April 2016 (UTC)

History: naming and isolation
The article reads:

"The toxin was first isolated and named in 1909 by Japanese scientist Dr. Yoshizumi Tahara"

But the linked source includes the following:

"Tetrodotoxin was named around 1911 after searching for active ingredient in fugu ovaries (83). Isolation of the chemical was achieved in the 1950s."

That's confusing, and probably should be fixed. -- Defanor (talk) 14:11, 14 July 2017 (UTC)

There is US1058643 patent, which appears to support what the article claims. -- Defanor (talk) 14:47, 14 July 2017 (UTC)
 * I've added 2 references to support the 1909 date (which is indeed "around 2011", so these are not inconsistent). From one of these we have "In July 1894, Dr. Yoshizumi Tahara presented the poison isolated from aqueous extract of ovaries of globefish at the monthly meeting of the Pharmaceutical Society of Japan. Later, he established an improved method for extraction and purification suitable for large-scale production of the poison. Finally, in 1909, he confirmed that globefish contains only one toxic substance and named it tetrodotoxin"

- Lago et al., 2015 Klbrain (talk) 14:48, 14 July 2017 (UTC)

Tetrodotoxin not produced by Taricha granulosa
I note the following article: http://faculty.virginia.edu/brodie/files/publications/toxicon2004a.pdf

No evidence for an endosymbiotic bacterial origin of tetrodotoxin in the newt Taricha granulosa Elizabeth M. Lehmana,*, Edmund D. Brodie Jr.b, Edmund D. Brodie IIIa a Department of Biology, Indiana University, Bloomington, Indiana 47405, USA b Department of Biology, Utah State University, Logan, Utah 84322, USA

Thank you, — Preceding unsigned comment added by 98.206.142.202 (talk) 17:29, 28 September 2017 (UTC)
 * Reference added in support of claim already in the text - this point is already made using more recent (2011 rather than 2004) sources). Klbrain (talk) 14:51, 30 September 2017 (UTC)

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2016 development rerenced to 2011 text
There is an issue that I have temporarily marked with hidden text in the section Tetrodotoxin where a statement/development "as of 2016" is referenced to a 2011 source. Presumably, a better source is available. Thanks for any insights on this. Samsara 08:41, 1 March 2018 (UTC)
 * Agree that the date claim isn't supported by the reference, so removed the "as of 2016" claim. I note that references later in the text do push this back to 2015, but also discuss contradictory evidence - so, better not to make an unreferenced claim at the start of the section. Klbrain (talk) 10:35, 2 March 2018 (UTC)

U2 Pilot Gary Powers
The US U2 pilot Gary Powers shot down over the Soviet Union had on him, a hollowed-out US coin containing a needle coated with TTX. 139.138.69.196 (talk) 04:34, 11 April 2018 (UTC)
 * Interesting, but the reference I've seen suggests that it was saxitoxin rather than TTX. — Preceding unsigned comment added by Klbrain (talk • contribs) 22:05, 11 April 2018 (UTC)

Gary Powers
He carried a needle impregnated with TTX inside a hollowed out US nickel when he was shot down by the Soviet Union. He had a special ring to open the Nickel. 2600:1700:1DC0:8CC0:C2CB:38FF:FE11:20F8 (talk) 20:31, 29 July 2018 (UTC)

Typo help
I can't find any source indicating "potenty" is a recognized word, and it's not clear to me what the intended meaning was in the sentence where it's used in the article. Who can make a better determination and correct it accordingly? Intchanter (talk) 16:27, 30 January 2019 (UTC)
 * I've had a go at rewording - I don't think that any technical concept was meant here; rather, it seemed to be an awkward use of "potent". Klbrain (talk) 17:07, 1 February 2019 (UTC)
 * Potency 2A00:23C5:EC86:E801:55C9:F7C8:22A9:B1A0 (talk) 14:28, 23 May 2022 (UTC)

Pufferfish, Takifugu Obscurus or general Tetraodontidae?
Ln. 82, * Aeromonas species from the puffer fish, Takifugu obscurus,
 * 1) Sources in nature,

Using a binomial name for a very specific species of pufferfish here seems off, particularly as no other species are listed. AFAIK most species, not only T. Obscurus, contain tetrodotoxin (unless explcitly bred to be safe).

Szincij (talk) 20:08, 15 June 2020 (UTC)