Abnormalities of GABA System and Human Pharmacoresistant Epilepsy

  • Sandra Orozco-Suárez
  • David Escalante-Santiago
  • Iris Angélica Feria-Romero
  • Monica E. Ureña-Guerrero
  • Luisa Rocha
  • Mario A. Alonso-Vanegas
  • Juana Villeda-Hernandez
  • Ana Luisa Velasco


Despite the availability of various newly developed antiepileptic drugs (AEDs), pharmacoresistance remains a major challenge in epilepsy management. Unraveling the mechanisms underlying AED resistance has been the focus of intense efforts, in order to develop new rationally designed therapies for as yet refractory epilepsies. Based on experimental and clinical studies, one of the major neurobiological theories that has been put forward is the target hypothesis, which suggests that AEDs are not effective because of target alterations in the epileptogenic brain. Several studies have shown that seizure activity results in altered expression of gamma-aminobutyric acid (GABA) components such as GABA transporters (GATs) and GABA receptors. Indeed, changes in the composition of subunits expression appear to affect the functioning of GABAergic neurotransmission. Here, we review the current literature on epilepsy-associated changes in the GABA system conducted in experimental models and observations made in patients with treatment-resistant epilepsy, as well as genetic abnormalities in the GABA system in refractory human epilepsy.


Pharmacoresistant epilepsy GABA neurotransmission GABA ­receptors Human data Animal models GABA subunits Antiepileptic drugs 



This study was supported by the Research in Health Found, FIS/IMSS/PROT/548 grant and National Council for Sciences and Technology of Mexico (Grant 98386). We thank Dr. Erika Brust-Mascher for English improvement.


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Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Sandra Orozco-Suárez
    • 1
  • David Escalante-Santiago
    • 1
  • Iris Angélica Feria-Romero
    • 1
  • Monica E. Ureña-Guerrero
    • 2
  • Luisa Rocha
    • 3
  • Mario A. Alonso-Vanegas
    • 4
  • Juana Villeda-Hernandez
    • 5
  • Ana Luisa Velasco
    • 6
  1. 1.Medical Research Unit in Neurological DiseasesNational Medical Center, “Siglo XXI”, IMSS Hospital of SpecialitiesMexico CityMexico
  2. 2.Departamento de Biología Celular y Molecular, Centro Universitario de Ciencias Biológicas y AgropecuariasUniversidad de GuadalajaraZapopanMexico
  3. 3.Department of PharmacobiologyCenter for Research and Advanced StudiesMexico CityMexico
  4. 4.ABC Hospital, Santa Fé, Neurology Center, and National Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”Mexico CityMexico
  5. 5.Pathology DepartmentNational Institute of Neurology and Neurosurgery “Manuel Velasco Suárez”Mexico CityMexico
  6. 6.Department of Neurology and NeurosurgeryGeneral Hospital of MexicoMexico CityMexico

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