Tarichatoxin—Tetrodotoxin: A Potent Neurotoxin

Abstract

Tarichatoxin, the neurotoxin first observed by Twitty in the embryos of the California newt Taricha torosa in 1934, has been obtained in crystalline form. It was identical to tetrodotoxin, isolated from the liver and ovaries of the Japanese puffer fish Sphoeroides rubripes. Thus, except in biogenetic studies where the origin of the toxin in amphibians is of importance, the name tetrodotoxin should be used for this substance, since this name has historical priority. The toxin was observed only in amphibians of the family Salamandridae and in fishes of the suborder Tetraodontoidae. Tetrodotoxin, or tarichatoxin, is one of the most toxic nonprotein substances known and has a mechanism of action resembling that of local anesthetics. However, the minimum detectably effective dose of the toxin is only 1/160,000 the minimum detectably effective dose of cocaine. The chemical structure of tetrodotoxin has been defined recently within narrow limits by two groups of Japanese workers, from classical chemical data and from X-ray crystallographic data on 2 derivatives. Objections were raised to the bridgehead amide structure, and an alternate zwitterion-ortho ester structure was proposed.