Comparison of tertiary and quaternary amine local anesthetics in their ability to depress membrane ionic conductances

Abstract

Tertiary and quaternary amine local anesthetics have been studied to determine their effect on membrane ionic conductances in squid giant axons. The tertiary compounds 6211 and 6603 (10mM), both lidocaine derivatives, suppressed both peak transient and steady‐state currents from either side of the nerve membrane. The time for the transient current to reach its peak was not appreciably affected. When applied internally, two quaternary compounds, QX‐314 and hemicholinium‐3 (1mM), were effective in suppressing both components of the membrane currents. However, when applied externally, they had no effect on the membrane currents even at a concentration of 10mM. The time to peak current was slightly prolonged when QX‐314 was applied internally. Another quaternary compound QX‐572 suppressed both currents from outside, but was more effective from the inside, 1mM externally being roughly equipotent to 0.1mM internally. The tertiary and quaternary compounds used in the present study block the nerve conduction by essentially the same mechanism as that previously reported for other local anesthetics.