Fig. 1. Tonic inhibition of Na+currents by amitriptyline and its permanently charged derivative N -methyl amitriptyline. The Na+channel–blocking effects of these drugs were studied with a reverse Na+gradient. (A ) Pulse protocol. Holding potential was −140 mV, and duration of the test pulse at 30 mV was 4.4 ms. Pulse interval was 30 sec. (B ) Steady-state concentration was achieved with amitriptyline within approximately 2 min but still had not occurred with N -methyl amitriptyline at approximately 15 min.