Tetrodotoxin

Tetrodotoxin is a potent neurotoxin classified as a guanidinium alkaloid. It occurs in several animals, most famously in pufferfish (fugu), where it concentrates in organs such as the liver, ovaries, and intestines. In some species it is produced by symbiotic bacteria and accumulates in the host. The toxin is not produced by plants or mammals they infect.

Tetrodotoxin acts by binding with high affinity to voltage-gated sodium channels in nerve and muscle membranes, blocking sodium influx and preventing action potential initiation and propagation. This leads to rapid impairment of sensory and motor function, with consciousness usually preserved early on. The toxin is highly specific to sodium channels and does not meaningfully affect other ion channels.

Symptoms typically begin with perioral numbness and tingling, followed by weakness, dizziness, nausea, and vomiting. As the dose increases, ataxia, hypotension, bradycardia, and respiratory failure may develop. Onset is usually within 10 to 60 minutes after ingestion, but timing can vary. Severe poisoning can be fatal if respiratory or cardiac arrest occurs.

Exposure risks are greatest from eating improperly prepared pufferfish or other contaminated seafood. There is no widely available antidote for tetrodotoxin. Treatment is supportive and includes airway protection, assisted ventilation if needed, monitoring, and managing cardiovascular instability. Activated charcoal may be considered if ingestion was recent. With prompt supportive care, some patients recover over hours to days, but outcomes depend on dose and rapidity of treatment.