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GABA A Receptor Subtypes: Therapeutic Potential in Down Syndrome, Affective Disorders, Schizophrenia, and Autism

Rudolph, Uwe ; Möhler, Hanns

Annual review of pharmacology and toxicology, 2014, Vol.54 (1), p.483-507 [Periódico revisado por pares]

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  • Título:
    GABA A Receptor Subtypes: Therapeutic Potential in Down Syndrome, Affective Disorders, Schizophrenia, and Autism
  • Autor: Rudolph, Uwe ; Möhler, Hanns
  • É parte de: Annual review of pharmacology and toxicology, 2014, Vol.54 (1), p.483-507
  • Descrição: The γ-aminobutyric acid (GABA) system plays a pivotal role in orchestrating the synchronicity of local networks and the functional coupling of different brain regions. Here we review the impact of the GABA A receptor subtypes on cognitive and emotional behavior, paying particular attention to five disease states: cognitive dysfunction and Down syndrome, anxiety disorders, depression, schizophrenia, and autism. Through the bidirectional modulation of tonic inhibition, α 5 -subunit-containing GABA A receptors permit the bidirectional modulation of cognitive processes, and a partial inverse agonist acting at the α 5 -subunit-containing GABA A receptor is in a clinical trial in individuals with Down syndrome. With regard to anxiety disorders, the viability of nonsedative anxiolytics based on the modulation of α 2 - and α 3 -subunit-containing GABA A receptors has been established in clinical proof-of-concept trials. Regarding the remaining three disease states, the GABA hypothesis of depression offers new options for antidepressant drug development; cognitive symptoms in schizophrenia are attributed to a cortical GABAergic deficit, and dysfunctional GABAergic inhibition is increasingly understood to contribute to the pathophysiology of autism spectrum disorders.
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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