Targeting NMDA Receptor Complex in Management of Epilepsy

Shravan Sivakumar; Mehdi Ghasemi; Steven C Schachter

doi:10.3390/ph15101297

Targeting NMDA Receptor Complex in Management of Epilepsy

Pharmaceuticals (Basel). 2022 Oct 21;15(10):1297. doi: 10.3390/ph15101297.

Authors

Shravan Sivakumar¹, Mehdi Ghasemi¹, Steven C Schachter^{2

3

4}

Affiliations

¹ Department of Neurology, University of Massachusetts Chan Medical School, Worcester, MA 01655, USA.
² Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
³ Harvard Medical School, Boston, MA 02114, USA.
⁴ Consortia for Improving Medicine with Innovation & Technology (CIMIT), Boston, MA 02114, USA.

Abstract

N-methyl-D-aspartate receptors (NMDARs) are widely distributed in the central nervous system (CNS) and play critical roles in neuronal excitability in the CNS. Both clinical and preclinical studies have revealed that the abnormal expression or function of these receptors can underlie the pathophysiology of seizure disorders and epilepsy. Accordingly, NMDAR modulators have been shown to exert anticonvulsive effects in various preclinical models of seizures, as well as in patients with epilepsy. In this review, we provide an update on the pathologic role of NMDARs in epilepsy and an overview of the NMDAR antagonists that have been evaluated as anticonvulsive agents in clinical studies, as well as in preclinical seizure models.

Keywords: N-methyl-D-aspartate (NMDA) receptor; NMDA receptor antagonist; clinical trial; epilepsy; seizure.

Publication types

Review

Grants and funding

M.G. is supported by a clinical research training scholarship in ALS funded by The ALS Association and The American Brain Foundation, in collaboration with the American Academy of Neurology, and an NIH-funded Wellstone fellowship training grant (NIH 5P50HD060848-15) for research on FSHD.