Tetrodotoxin

Tetrodotoxin (TTX) is a very effective poison, inhibitingly acting on voltage-gated sodium channels, thereby  preventing the formation of an action potential on the membranes of neurons. It is a thermostable substance that is soluble in water.

Although this neurotoxin is undoubtedly synthesized by bacteria, it has been isolated from a number of animals, including the Japanese Fugu  fish. is responsible for the presence of the toxin in the organs (especially the liver, gonads and skin) of Fugu   Specifically, the bacterium  Vibrio alginolyticus  fish.

Mechanism of action
Tetrodotoxin binds with high potency already at nanomolar concentrations (5–15 nM) especially to sodium channels in nervous tissue and skeletal muscle , while the myocardium is more resistant and sodium channel blocking only occurs at a concentration of ~10  −5  M. The toxin binds to α-subunit, which consists of four repeating domains (I–IV). Each domain consists of another six segments (S1–S6), in this case the toxin binds to amino acids in the so-called P-loop  between segments S5–S6 of domain I, which protrudes above the outer mouth of the channel. These P-loops  are present in all four domains, forming the outer entrance to the ion channel.

Toxicity
TTX poisoning can occur through ingestion, inhalation, injection, or even through skin abrasions. The LD 50  in mice is reported to be 334 μg/kg when administered per os, while the lethal dose is only 8 μg/kg when injected. .TTX poisoning occurs in humans especially after eating improperly prepared Fugu fish,  which is a sought-after culinary specialty. The course of poisoning depends on the ingested dose. During the first 30 minutes of ingestion, poisoning is manifested by gradual numbness, first of the lips and tongue, later of the limbs, but if the dose is fatal, the symptoms appear earlier. There is weakness, loss of coordination, nausea, lethargy and gradually paralysis, with higher doses cardiac arrhythmia may occur. The affected person does not always have to fall into a coma - he can be completely conscious. The cause of death is respiratory muscle failure, depending on the ingested dose, after 8 hours.

Treatment
Since there is no antidote , the treatment is  symptomatic. After ingestion, the amount of absorbed TTX can be reduced in the emergency room by gastric lavage and administration of activated charcoal. If the person survives acute poisoning, they will fully recover within a few days without any consequences. During experiments on mice, it was possible to prepare effective specific monoclonal antibodies against TTX, but this method has not yet been tested in humans.

Usage
TTX has been tested as an analgesic for cancer patients, with a demonstrable positive effect on pain relief. A clinical trial has also been established to demonstrate that TTX alleviates withdrawal symptoms in heroin withdrawal syndrome