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Tetrodotoxin: A New Strategy to Treat Visceral Pain?
Review

From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic

1
Department of Ecology and Evolutionary Biology & UCLA La Kretz Center for California Conservation Science, Institute of the Environment and Sustainability, University of California, Los Angeles, CA 90095, USA
2
Natural Science Division, Pepperdine University, Malibu, CA 90263, USA
3
Department of Integrative Biology, Michigan State University, East Lansing, MI 48824, USA
*
Author to whom correspondence should be addressed.
The authors contributed equally to this manuscript.
Toxins 2021, 13(8), 517; https://doi.org/10.3390/toxins13080517
Received: 21 June 2021 / Revised: 17 July 2021 / Accepted: 20 July 2021 / Published: 24 July 2021
(This article belongs to the Special Issue Tetrodotoxin (TTX) as a Therapeutic Agent)
Tetrodotoxin (TTX) is a potent neurotoxin that was first identified in pufferfish but has since been isolated from an array of taxa that host TTX-producing bacteria. However, determining its origin, ecosystem roles, and biomedical applications has challenged researchers for decades. Recognized as a poison and for its lethal effects on humans when ingested, TTX is primarily a powerful sodium channel inhibitor that targets voltage-gated sodium channels, including six of the nine mammalian isoforms. Although lethal doses for humans range from 1.5–2.0 mg TTX (blood level 9 ng/mL), when it is administered at levels far below LD50, TTX exhibits therapeutic properties, especially to treat cancer-related pain, neuropathic pain, and visceral pain. Furthermore, TTX can potentially treat a variety of medical ailments, including heroin and cocaine withdrawal symptoms, spinal cord injuries, brain trauma, and some kinds of tumors. Here, we (i) describe the perplexing evolution and ecology of tetrodotoxin, (ii) review its mechanisms and modes of action, and (iii) offer an overview of the numerous ways it may be applied as a therapeutic. There is much to be explored in these three areas, and we offer ideas for future research that combine evolutionary biology with therapeutics. The TTX system holds great promise as a therapeutic and understanding the origin and chemical ecology of TTX as a poison will only improve its general benefit to humanity. View Full-Text
Keywords: tetrodotoxin; TTX; neurotoxin; sodium channel; analgesic; therapeutic; evolutionary medicine tetrodotoxin; TTX; neurotoxin; sodium channel; analgesic; therapeutic; evolutionary medicine
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MDPI and ACS Style

Bucciarelli, G.M.; Lechner, M.; Fontes, A.; Kats, L.B.; Eisthen, H.L.; Shaffer, H.B. From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic. Toxins 2021, 13, 517. https://doi.org/10.3390/toxins13080517

AMA Style

Bucciarelli GM, Lechner M, Fontes A, Kats LB, Eisthen HL, Shaffer HB. From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic. Toxins. 2021; 13(8):517. https://doi.org/10.3390/toxins13080517

Chicago/Turabian Style

Bucciarelli, Gary M., Maren Lechner, Audrey Fontes, Lee B. Kats, Heather L. Eisthen, and H. B. Shaffer 2021. "From Poison to Promise: The Evolution of Tetrodotoxin and Its Potential as a Therapeutic" Toxins 13, no. 8: 517. https://doi.org/10.3390/toxins13080517

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