Targeting metabotropic glutamate receptors in the treatment of epilepsy: Rationale and current status
| Autor: | Ferdinando Nicoletti, Roberta Celli, Ines Santolini, Valeria Bruno, Richard Teke Ngomba, Gilles van Luijtelaar |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Clinical Biochemistry absence seizures macromolecular substances Receptors Metabotropic Glutamate Synaptic Transmission 03 medical and health sciences Epilepsy 0302 clinical medicine Drug Discovery medicine Animals Humans Molecular Targeted Therapy Pharmacology convulsive seizures epilepsy Metabotropic glutamate receptors business.industry Action intention and motor control Glutamate receptor medicine.disease 030104 developmental biology Convulsive Seizures Targeted drug delivery Epilepsy Absence Metabotropic glutamate receptor 030220 oncology & carcinogenesis Molecular Medicine GABAergic Anticonvulsants business Neuroscience |
| Zdroj: | Expert Opinion on Therapeutic Targets, 23, 4, pp. 341-351 Expert Opinion on Therapeutic Targets, 23, 341-351 |
| ISSN: | 1472-8222 |
| Popis: | Contains fulltext : 201991.pdf (Publisher’s version ) (Open Access) 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. 11 p. |
| Databáze: | OpenAIRE |
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