PHARMACOLOGY OF TETRODOTOXIN

Tetrodotoxin (TTX) is a potent neurotoxin originally found in the ovary and liver of puffer fish. It has now become abundantly clear that TTX is not synthesized in the puffer fish, and that it is produced by certain bacteria and reaches the fish via the food chain. The pharmacology of TTX had been studied for a long period of time especially in Japan as puffer fish is regarded as the most delicious fish among Japanese. However, since the pioneering discovery of the selective and potent blocking action of TTX on the sodium channel, extensive investigations by a number of scientists into its cellular and molecular mechanism of action have been launched. Equally important is the fact that TTX has since then been used extensively as a chemical tool in the laboratory for the purpose of studying the sodium channel, other ion channels, and various aspects of membrane excitability and synaptic transmission. The highlights of the recent studies of TTX are given in this chapter. Older literature is not discussed as it has been reviewed many times by a number of investigators. Readers are encouraged to consult with these review articles. Thus the present chapter covers the recent developments in the areas of the sources of TTX, the mechanisms of action on sodium channels, TTX-resistant sodium channels, the site of action and binding of TTX, and therapeutic applications of TTX. Saxitotoxin, a paralytic shellfish toxin, which exhibits the same sodium channel blocking action is also described.