This study aimed at evaluating the effects of
eslicarbazepine,
carbamazepine (CBZ),
oxcarbazepine (OXC) and
lacosamide (LCM) on the fast and slow inactivated states of
voltage-gated sodium channels (VGSC). The anti-epileptiform activity was evaluated in mouse isolated hippocampal slices. The
anticonvulsant effects were evaluated in MES and the 6-Hz psychomotor tests. The whole-cell patch-clamp technique was used to investigate the effects of
eslicarbazepine, CBZ, OXC and LCM on
sodium channels endogenously expressed in N1E-115 mouse
neuroblastoma cells. CBZ and
eslicarbazepine exhibit similar concentration dependent suppression of epileptiform activity in hippocampal slices. In N1E-115 mouse
neuroblastoma cells, at a concentration of 250 μM, the voltage dependence of the fast inactivation was not influenced by
eslicarbazepine, whereas LCM, CBZ and OXC shifted the V0.5 value (mV) by -4.8, -12.0 and -16.6, respectively.
Eslicarbazepine- and LCM-treated fast-inactivated channels recovered similarly to control conditions, whereas CBZ- and OXC-treated channels required longer pulses to recover. CBZ,
eslicarbazepine and LCM shifted the voltage dependence of the slow inactivation (V0.5, mV) by -4.6, -31.2 and -53.3, respectively. For
eslicarbazepine, LCM, CBZ and OXC, the affinity to the slow inactivated state was 5.9, 10.4, 1.7 and 1.8 times higher than to the channels in the resting state, respectively. In conclusion,
eslicarbazepine did not share with CBZ and OXC the ability to alter fast inactivation of VGSC. Both
eslicarbazepine and LCM reduce VGSC availability through enhancement of slow inactivation, but LCM demonstrated higher interaction with VGSC in the resting state and with fast inactivation gating.