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Year : 1998  |  Volume : 30  |  Issue : 5  |  Page : 277-298

The NMDA receptor in epilepsy

Correspondence Address:
Manocha Anshu

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Source of Support: None, Conflict of Interest: None

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N-methyl-D-aspartate(NMDA) receptors have been the target of a large number of studies, and the field of research is still rapidly growing. Many in vivo and in vitro studies support the hypothesis that NMDA receptors contribute to the development and expression of epilepsy and play a pivotal role in induction of synaptic plasticity i.e. long-term potentiation (LTP). Decreasing glutamatergic neurotransmission pro-vides rational therapeutic approaches to epilepsy. Potent anticonvulsant effects are seen with the acute administration of NMDA antagonists in a wide range of animal models. NMDA receptors are important potential targets for the development of antiepileptic drugs. However, the early optimism regarding competitive NMDA recognition site antagonists as antiepileptic drug candidates has been tempered by the recognition that such antagonists have significant toxicities. Several other approaches to NMDA receptor blockade appear promising, including competitive antagonism at the glycine site and low-affinity channel blockade. In addition, there is interest in NMDA-associated polyamine-and redox sites but clearly further work is required to address this issue. Interestingly, molecular biology studies of NMDA receptor have revealed multiplicity in this receptor subtypes and NMDA receptor subunit, NR1 and NR2 represent heterogeneity in this receptor. Certain classes of NMDA receptor antagonists are selective for specific subunit combinations.This is an area with promising scope in future for pharmacological exploitation, for instance, designing antagonists that are selective for subunit combinations that might show an increased expression during epileptogenesis. There are, however, many important questions that remain only partly answered and probably many more surprises ahead.


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