Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status

Roberta Celli, Ines Santolini, Gilles Van Luijtelaar, Richard T Ngomba, Valeria Bruno, Ferdinando Nicoletti

Research output: Contribution to journalArticlepeer-review


INTRODUCTION: Several drugs targeting the GABAergic system are used in the treatment of epilepsy, but only one drug targeting glutamate receptors is on the market. This is surprising because an imbalance between excitatory and inhibitory neurotransmission lies at the core of the pathophysiology of epilepsy. One possible explanation is that drug development has been directed towards the synthesis of molecules that inhibit the activity of ionotropic glutamate receptors. These receptors mediate fast excitatory synaptic transmission in the central nervous system (CNS) and their blockade may cause severe adverse effects such as sedation, cognitive impairment, and psychotomimetic effects. Metabotropic glutamate (mGlu) receptors are more promising drug targets because these receptors modulate synaptic transmission rather than mediate it. Areas covered: We review the current evidence that links mGlu receptor subtypes to the pathophysiology and experimental treatment of convulsive and absence seizures. Expert opinion: While mGlu5 receptor negative allosteric modulators have the potential to be protective against convulsive seizures and hyperactivity-induced neurodegeneration, drugs that enhance mGlu5 and mGlu7 receptor function may have beneficial effects in the treatment of absence epilepsy. Evidence related to the other mGlu receptor subtypes is more fragmentary; further investigations are required for an improved understanding of their role in the generation and propagation of seizures.

Original languageEnglish
Pages (from-to)341-351
Number of pages11
JournalExpert Opinion on Therapeutic Targets
Issue number4
Publication statusPublished - Apr 2019


Dive into the research topics of 'Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status'. Together they form a unique fingerprint.

Cite this