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Glutamate Receptors as Targets for Novel Antiepileptic Drug Therapy

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Antiepileptic Drug Discovery

Part of the book series: Methods in Pharmacology and Toxicology ((MIPT))

Abstract

In recent years, extensive research has been directed towards the development of novel therapeutic targets in epilepsy. A number of studies have reported that glutamate plays an important role in seizure generation and spread. Glutamate is the predominant excitatory neurotransmitter in the brain, exerting its action through ionotropic and metabotropic receptors. Notably, a significant increase of extracellular glutamate release was observed in hippocampus during the ictal, postictal, and interictal period of patients with pharmacoresistant epilepsy undergoing surgery (During and Spencer, Lancet 341:1607–1610, 1993; Cavus et al., Epilepsia 49:1358–1366, 2008). These results indicate a strong association between increased glutamate and epileptiform activity. The chronic increase in extracellular glutamate release favors neuronal hyperexcitability and subsequent neuronal damage. Thus, the pharmacological blockade of glutamatergic signaling represents an attractive alternative for the control of seizures and neuroprotection. In particular, glutamate receptors are attractive targets for novel antiepileptic drugs because different studies have demonstrated that its agonists and antagonists reduce excessive excitatory responses providing neuroprotection and causing seizure suppression. We provide a brief description of the glutamate agonists and antagonists with potential effects on these receptors and the results obtained in both preclinical models of epilepsy and during clinical trials.

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Acknowledgments

We thank Heidy Higuera Hernández for her technical assistance.

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Authors and Affiliations

  1. Epilepsy Clinic, Unit of Functional Neurosurgery, Stereotaxy and Radiosurgery, General Hospital of Mexico “Dr. Eduardo Liceaga”, Dr. Balmis 148, Col. Doctores, Del. Cuauhtémoc C.P. 06726, Mexico City, Mexico

    Manola Cuéllar-Herrera, Daruni Vázquez-Barrón, Francisco Velasco & Ana L. Velasco

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Calz. Tenorios 235. Col. Granjas Coapa, Mexico City, 14330, Mexico

    César E. Santana-Gómez & Francia Carmona-Cruz

Authors
  1. Manola Cuéllar-Herrera
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  2. César E. Santana-Gómez
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  3. Francia Carmona-Cruz
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  4. Daruni Vázquez-Barrón
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  5. Francisco Velasco
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  6. Ana L. Velasco
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Correspondence to Manola Cuéllar-Herrera .

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Editors and Affiliations

  1. Laboratorio de Investigación y Desarrollo de Bioactivos (LIDeB) Faculty of Exact Sciences, National University of La Plata, La Plata, Buenos Aires, Argentina

    Alan Talevi

  2. Department of Pharmacobiology, Center for Research and Advanced Studies, Mexico City, Mexico

    Luisa Rocha

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Cuéllar-Herrera, M., Santana-Gómez, C.E., Carmona-Cruz, F., Vázquez-Barrón, D., Velasco, F., Velasco, A.L. (2016). Glutamate Receptors as Targets for Novel Antiepileptic Drug Therapy. In: Talevi, A., Rocha, L. (eds) Antiepileptic Drug Discovery. Methods in Pharmacology and Toxicology. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6355-3_6

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