A substantial amount of research has shown that N-methyl-D-aspartate receptors (NMDARs) may play a key role in the pathophysiology of several neurological diseases, including epilepsy. Animal models of epilepsy and clinical studies demonstrate that NMDAR activity and expression can be altered in association with epilepsy and particularly in some specific seizure types. NMDAR antagonists have been shown to have antiepileptic effects in both clinical and preclinical studies. There is some evidence that conventional antiepileptic drugs may also affect NMDAR function. In this review, we describe the evidence for the involvement of NMDARs in the pathophysiology of epilepsy and provide an overview of NMDAR antagonists that have been investigated in clinical trials and animal models of epilepsy.
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