Differential effect of antiseizure medications eslicarbazepine and carbamazepine on hippocampal synaptic transmission and plasticity

Anti-seizure medication (ASM) is the most widely used treatment for patients with epilepsy (PWE). Despite the availability of multiple ASMs, about 30% of the patients become drug-resistant. Moreover, there are several cases of seizure aggravation and cognitive side effects associated with ASMs. Therefore, understanding how ASMs work is essential for improving epilepsy treatment. In this study, we investigated the effect of first-generation drug carbamazepine (CBZ) and third-generation drug eslicarbazepine acetate (ESL) on neuronal excitability, synaptic transmission and synaptic plasticity in the hippocampal neurons using patch clamp and field recording experiments. We found that both ESL and CBZ reduced the neuronal excitability differently. ESL reduced the action potential amplitude but did not affect the firing frequency, whereas CBZ application not only reduced the amplitude but also led to a significant reduction in the firing frequency. ESL reduced the amplitude of both spontaneous EPSCs and IPSCs, but CBZ did not alter spontaneous synaptic activity. Further, ESL reduced the magnitude of LTP in Schaffer collateral CA1 synapses but CBZ did not alter LTP. LTD was also studied to understand the effect of the drugs on bidirectional plasticity. We found that both ESL and CBZ reduced LTD, but the impairment caused by ESL was stronger than that caused by CBZ. This study underlines the complexity of the mechanism of action of ASM and also highlights the need for further research to develop better targeted drugs for epilepsy treatment.