Abstract Carbamazepine (5H-dibenz[b,f]azepine-5-carboxamide) and oxcarbazepine (10,11-dihydro-10-oxo-5H-dibenz[b,f]azepine-5-carboxamide) are widely used for the treatment of partial epilepsy. Recent work indicates that these drugs, in addition to targeting voltage-gated Na + channels, can modulate ligand-gated channels. These compounds appear to be particularly effective for treatment of nocturnal frontal lobe epilepsy, which can be caused by mutant neuronal nicotinic receptors. We compared the effects of carbamazepine and oxcarbazepine on heteromeric nicotinic receptors to better understand the underlying mechanism of the effect of these drugs in epileptic patients. Receptors were expressed in cell lines and studied by patch-clamp methods at − 60 mV. For α2β4 receptors activated with 100 μM nicotine, IC 50 for carbamazepine was 49 μM. Receptors in which α2 was substituted with α2-I279N, linked to autosomal dominant nocturnal frontal lobe epilepsy, had an IC 50 of 21 μM. For oxcarbazepine, the IC 50 was larger than 500 μM for wild-type receptors and approximately 100 μM for mutant receptors. A similar inhibition was observed in the presence of 10 μM nicotine, indicating a non-competitive mechanism. The monohydroxy derivative (MHD) of oxcarbazepine, clinically the most relevant compound, was tested on both α2β4 and α4β2 receptors, to obtain a broader view of its possible physiological effects. At the typical concentration present in blood (100 μM), MHD produced an approximate 40% channel block on α4β2, but no significant effect on α2β4 receptors. Oxcarbazepine and MHD retarded the channel deactivation, suggesting that these compounds produce open channel block. These results may explain the particular efficacy of these drugs in nocturnal frontal lobe epilepsy.