The actions of the neuroprotective and anticonvulsant agent riluzole on voltage-activated currents were studied in primary cultures of rat cortical neurons by using whole-cell patch-clamp recording techniques. Isolated Na+, Ca2+ and K+ currents were generated in these cells by depolarizing commands from a holding potential of - 80 mV. Riluzole (10-300 microM) reversibly reduced in a dose-dependent manner the inward Na+ currents with an IC50 of 51 microM in all the tested neurons (n=29). This drug also shifted the steady-state inactivation curve of the sodium current towards more negative values (about 20mV, n=15) while it did not change significantly the decay phase of the Na+ current. Furthermore, riluzole (100 and 300 microM; n=5 and n=3, respectively) did not modulate the inward Ca2+ currents evoked by depolarizing steps on cortical cells. An additional concentration-dependent effect of riluzole was observed on the outward potassium currents. In fact, while the amplitude of the peak of the outward current (IA) was not changed significantly, the amplitude of the late component of the outward K+ current (Iss) was markedly decreased during the perfusion of riluzole (IC50=88 microM; n=16). It is concluded that riluzole modulates the Na+- and the late K+-dependent currents in cortical neurons. Both phenomena may explain, at least in part, the anticonvulsant and neuroprotective properties of this compound.