Chapter 24 Glutamate receptors in epilepsy

Abstract

Glutamatergic synapses play a critical role in all epileptic phenomena. Broadly enhanced activation of post-synaptic glutamate receptors (ionotropic and metabotropic) is proconvulsant. Antagonists of NMDA receptors and AMPA receptors are powerful anticonvulsants in many animal models of epilepsy. A clinical application of pure specific glutamate antagonists has not yet been established. Many different alterations in glutamate receptors or transporters can potentially contribute to epileptogenesis. Several genetic alterations have been shown to be epileptogenic in animal models but no specific mutation relating to glutamatergic function has yet been linked to a human epilepsy syndrome. There is clear evidence for altered NMDA receptor function in acquired epilepsy in animal models and in man. Changes in metabotropic receptor function may also play a key role in epileptogenesis.