Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin.

[1][2] Although it produces thousands of intoxications annually and several deaths,[3] it has shown efficacy for the treatment of cancer-related pain in phase II and III clinical trials.

[5] Its mechanism of action – selective blocking of the sodium channel – was shown definitively in 1964 by Toshio Narahashi and John W. Moore at Duke University, using the sucrose gap voltage clamp technique.

[6] Apart from their bacterial species of most likely ultimate biosynthetic origin (see below), tetrodotoxin has been isolated from widely differing animal species, including:[1] Tarichatoxin was shown to be identical to TTX in 1964 by Mosher et al.,[12][13] and the identity of maculotoxin and TTX was reported in Science in 1978,[14] and the synonymity of these two toxins is supported in modern reports (e.g., at Pubchem[15] and in modern toxicology textbooks[16]) though historic monographs questioning this continue in reprint.

[18] Even though the toxin acts as a defense mechanism, some predators such as the common garter snake have developed insensitivity to TTX, which allows them to prey upon toxic newts.

"[2] TTX-producing bacteria include Actinomyces, Aeromonas, Alteromonas, Bacillus, Pseudomonas, and Vibrio species;[2] in the following animals, specific bacterial species have been implicated:[a] The association of bacterial species with the production of the toxin is unequivocal – Lago and coworkers state, "[e]ndocellular symbiotic bacteria have been proposed as a possible source of eukaryotic TTX by means of an exogenous pathway",[2] and Chau and coworkers note that the "widespread occurrence of TTX in phylogenetically distinct organisms... strongly suggests that symbiotic bacteria play a role in TTX biosynthesis"[1] – although the correlation has been extended to most but not all animals in which the toxin has been identified.

[1][2][5] To the contrary, there has been a failure in a single case, that of newts (Taricha granulosa), to detect TTX-producing bacteria in the tissues with highest toxin levels (skin, ovaries, muscle), using PCR methods,[24] although technical concerns about the approach have been raised.

[30][31] The prevalence of TTX-s Na+ channels in the central nervous system makes tetrodotoxin a valuable agent for the silencing of neural activity within a cell culture.

They consist of different amino acid substitutions in similar positions, a weak example of convergent evolution caused by how TTX binds to the unmutated VGSC.

[53] The therapeutic uses of puffer fish (tetraodon) eggs were mentioned in the first Chinese pharmacopoeia Pen-T’so Ching (The Book of Herbs, allegedly 2838–2698 BC by Shennong; but a later date is more likely), where they were classified as having "medium" toxicity, but could have a tonic effect when used at the correct dose.

[30] In the Pen-T’so Kang Mu (Index Herbacea or The Great Herbal by Li Shih-Chen, 1596) some types of the fish Ho-Tun (the current Chinese name for tetraodon) were also recognized as both toxic yet, at the right dose, useful as part of a tonic.

)[54] The German physician Engelbert Kaempfer, in his "A History of Japan" (translated and published in English in 1727), described how well known the toxic effects of the fish were, to the extent that it would be used for suicide and that the Emperor specifically decreed that soldiers were not permitted to eat it.

[51] On that date Cook recorded his crew eating some local tropic fish (pufferfish), then feeding the remains to the pigs kept on board.

In hindsight, it is clear that the crew survived a mild dose of tetrodotoxin, while the pigs ate the pufferfish body parts that contain most of the toxin, thus being fatally poisoned.

[51] Having pins and needles of the lips and tongue is followed by developing it in the extremities, hypersalivation, sweating, headache, weakness, lethargy, incoordination, tremor, paralysis, bluish skin, loss of voice, difficulty swallowing, and seizures.

The gastrointestinal symptoms are often severe and include nausea, vomiting, diarrhoea, and abdominal pain; death is usually secondary to respiratory failure.

[53][58] There is increasing respiratory distress, speech is affected, and the victim usually exhibits shortness of breath, excess pupil dilation, and abnormally low blood pressure.

[51] Alpha adrenergic agonists are recommended in addition to intravenous fluids to increase the blood pressure; anticholinesterase agents "have been proposed as a treatment option but have not been tested adequately".

There have been no confirmed cases of tetrodotoxicity from the Atlantic pufferfish, Sphoeroides maculatus, but three studies found extracts from fish of this species highly toxic in mice.

Several recent intoxications from these fishes in Florida were due to saxitoxin, which causes paralytic shellfish poisoning with very similar symptoms and signs.

[61] In 2009, a major scare in the Auckland Region of New Zealand was sparked after several dogs died eating Pleurobranchaea maculata (grey side-gilled seaslug) on beaches.

Subsequent careful analysis has however repeatedly called early studies into question on technical grounds, and failed to identify the toxin in any preparation.

Kao and Yasumoto concluded in the first of their papers in 1986 that "the widely circulated claim in the lay press to the effect that tetrodotoxin is the causal agent in the initial zombification process is without factual foundation.

[citation needed] Tetrodotoxin may be quantified in serum, whole blood or urine to confirm a diagnosis of poisoning in hospitalized patients or to assist in the forensic investigation of a case of fatal overdosage.

[85] This idea first appeared in the 1938 non-fiction book Tell My Horse by Zora Neale Hurston in which there were multiple accounts of purported tetrodotoxin poisoning in Haiti by a voodoo sorcerer called the bokor.

James Ellroy includes "blowfish toxin" as an ingredient in Haitian Vodou preparations to produce zombieism and poisoning deaths in his dark, disturbing, violent novel Blood's a Rover.