Potency difference between the zwitterion form and the cation forms of tetrodotoxin.

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.