An aminoperhydroquinazoline poison found mainly in the liver and ovaries of fishes in the order tetraodontiformes, which are eaten. Tetrodotoxin is a potent neurotoxin that is produced by bacteria (genus Pseudoalteromonas, Pseudomonas, Vibrio) and found in certain species of Tetraodontiformes (puffer fish, porcupine fish, ocean sunfish, triggerfish), from which its name is derived. It acts on the voltage-gated sodium channels of nerve cells. (1) The toxin causes paresthesia and paralysis through interference with neuromuscular conduction. Tetrodotoxin is being investigated by Wex Pharmaceuticals for the treatment of chronic and breakthrough pain in advanced cancer patients as well as for the treatment of opioid dependence.
belongs to the class of organic compounds known as tetrodotoxins. Tetrodotoxins are compounds structurally characterized by the presence of the tetrodotoxin skeleton, which is based on 5,7-(epoxymethanooxy)quinazolin-10-olate moiety.
Tetrodotoxin binds to what is known as site 1 of the fast voltage-gated sodium channel. Site 1 is located at the extracellular pore opening of the ion channel. The binding of any molecules to this site will temporarily disable the function of the ion channel. Saxitoxin and several of the conotoxins also bind the same site.
Metabolism
The metabolic source of tetrodotoxin is uncertain. No algal source has been identified, and until recently tetrodotoxin was assumed to be a metabolic product of the host. However, recent reports of the production of tetrodotoxin/anhydrotetrodotoxin by several bacterial species, including strains of the family Vibrionaceae, Pseudomonas sp., and Photobacterium phosphoreum, point toward a bacterial origin of this family of toxins (3).
No indication of carcinogenicity to humans (not listed by IARC).
Uses/Sources
For the treatment of chronic and breakthrough pain in advanced cancer patients as well as for the treatment of opioid dependence. Tetrodotoxin is produced by bacteria (genus Pseudoalteromonas, Pseudomonas, Vibrio) and found in certain species of Tetraodontiformes (puffer fish, porcupine fish, ocean sunfish, triggerfish), from which its name is derived. (1)
Minimum Risk Level
Not Available
Health Effects
Tetrodoxin is a potent neurotoxin and produces paralysis, which may be followed by death due to respiratory failure. (1)
Symptoms
Symptoms of tetrodoxin poisoning typically occur within 30 minutes of exposure and include paresthesias of the lips and tongue, sialorrhea, sweating, headache, weakness, lethargy, ataxia, uncoordination, tremor, paralysis, cyanosis, aphonia, dysphagia, seizures, dyspnoea, bronchorrhea, bronchospasm, respiratory failure, coma, and hypotension. Gastroenteric symptoms are often severe and include nausea, vomiting, diarrhoea, and abdominal pain. Cardiac arrhythmias may precede complete respiratory failure and cardiovascular collapse. (1)
Treatment
Treatment of tetrodoxin poisoning is supportive and symptomatic, with aggressive early airway management. In cases of ingestion gastric lavage and/or the administration of active charcoal may be performed. Alpha adrenergic agonists are recommended in addition to intravenous fluids to combat hypotension. (1)
