Potency Difference between the Zwitterion Form and the Cation Forms of Tetrodotoxin

Abstract

Tetrodotoxin can exist as a zwitterion or two different cations in aqueous solutions. The cation forms are more potent in nerve block. Thus the lactone-hemilactal configuration of tetrodotoxin influences potency. Electrostatic attraction, hydrogen bonding, and intermolecular hemilactal formation are possible mechanisms of interaction with membrane receptors.