The mechanism of action of local anesthesia by tetraethylammonium derivatives.

Tetraethylammonium (TEA+) derivatives in which one of the ethyl groups is replaced by a longer chain alkane (C4-C16) were tested for their ability to block the compound action potential (CAP) of frog sciatic nerve. A parabolic relation between chain length and 100 per cent blocking dose was found, suggesting an optimal size of C12 for the inhibitory receptor. Two types of inhibition were observed. Type 1 was an inhibition of the CAP at all frequencies when the nerve was perfused with the TEA+ derivative. Interaction with tetrodotoxin suggests this is a Na+ channel effect. Type 2 was an irreversible (still present after nerve wash) frequency-dependent inhibition that is distinct from and synergistic with Na+ channel blocking local anesthetics. From the kinetics of inhibition onset and transport studies, it is suggested that the ultralong action of the TEA+ derivatives is mediated by binding to a receptor at the internal part of K+ channels.