Revisiting AMPA receptors as an antiepileptic drug target

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

In the 1990s there was intense interest in ionotropic glutamate receptors as therapeutic targets for diverse neurological disorders, including epilepsy. NMDA receptors were thought to play a key role in the generation of seizures, leading to clinical studies of NMDA receptor blocking drugs in epilepsy. Disappointing results dampened enthusiasm for ionotropic glutamate receptors as a therapeutic target. Eventually it became appreciated that another type of ionotropic glutamate receptor, the AMPA receptor, is actually the predominant mediator of excitatory neurotransmission in the central nervous system and moreover that AMPA receptors are critical to the generation and spread of epileptic activity. As drugs became available that selectively target AMPA receptors, it was possible to demonstrate that AMPA receptor antagonists have powerful antiseizure activity in in vitro and in vivo models. A decade later, promising clinical studies with AMPA receptor antagonists, including the potent noncompetitive antagonist perampanel, are once again focusing attention on AMPA receptors as a drug target for epilepsy therapy.

Original languageEnglish (US)
Pages (from-to)56-63
Number of pages8
JournalEpilepsy Currents
Volume11
Issue number2
DOIs
StatePublished - Mar 2011

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AMPA Receptors
Anticonvulsants
Ionotropic Glutamate Receptors
Epilepsy
N-Methyl-D-Aspartate Receptors
Pharmaceutical Preparations
Nervous System Diseases
Synaptic Transmission
Seizures
Therapeutics
Central Nervous System

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Revisiting AMPA receptors as an antiepileptic drug target. / Rogawski, Michael A.

In: Epilepsy Currents, Vol. 11, No. 2, 03.2011, p. 56-63.

Research output: Contribution to journalArticle

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