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.
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects; D009407:Nerve Block; D011188:Potassium / Q000378:metabolism; D011894:Rana pipiens; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D013329:Structure-Activity Relationship; D013757:Tetraethylammonium Compounds / Q000378:metabolism / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D007473:Ion Channels; D013757:Tetraethylammonium Compounds; D013779:Tetrodotoxin; D012964:Sodium; D011188:Potassium