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Epilepsy is one of the most common neurological disorders and the administration of antiepileptic drugs (AEDs) is the most common treatment. Although there are more than 15 AEDs available, a third of epilepsy patients remain refractory to available drugs, so novel effective drugs are needed. Here, we found that DV21, which is a natural triterpenoid compound extracted from plants of the Asclepiadaceae family, significantly decreased the incidence and stages of seizures in three classical drug-induced acute seizure models in C57BL/6 mice. Furthermore, we also found that the antiepileptic effect of DV21 might be partly mediated through reducing the excitability of cortical pyramidal neurons by increasing M current, which are low-threshold non-inactivating voltage-gated potassium currents. Moreover, the application of XE991, an inhibitor of M current, could block most the antiepileptic effect of DV21. Taken together, our results indicated that DV21 might be a novel leading compound for the treatment of epilepsy.

DV21 decreases excitability of cortical pyramidal neurons and acts in epilepsy