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New Drug Treatments for Schizophrenia: A Review of Approaches to Target Circuit Dysfunction.
Howes, Oliver D; Dawkins, Eleanor; Lobo, Maria C; Kaar, Stephen J; Beck, Katherine.
Afiliación
  • Howes OD; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Institute of Clinical Sciences, Faculty of Medicine, Imperial College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, United Kingdom. Electr
  • Dawkins E; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, United Kingdom.
  • Lobo MC; South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, United Kingdom.
  • Kaar SJ; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; Division of Psychology and Mental Health, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom; Greater Manchester Mental Health Na
  • Beck K; Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom; South London and Maudsley NHS Foundation Trust, Maudsley Hospital, London, United Kingdom.
Biol Psychiatry ; 96(8): 638-650, 2024 Oct 15.
Article en En | MEDLINE | ID: mdl-38815885
ABSTRACT
Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side effects and have limited efficacy for many patients, highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, postmortem, genetic, and pharmacological studies have highlighted the key role of cortical GABAergic (gamma-aminobutyric acidergic)-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive, and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABAergic or glutamatergic targets, including glycine transporters, D-amino acid oxidase, sodium channels, or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system, such as muscarinic or trace amine receptors or 5-HT2A receptors, while PDE10A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy, and side effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If these drugs are approved for clinical use, they have the potential to revolutionize understanding of the pathophysiology and treatment of schizophrenia.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Antipsicóticos Límite: Animals / Humans Idioma: En Revista: Biol Psychiatry Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Esquizofrenia / Antipsicóticos Límite: Animals / Humans Idioma: En Revista: Biol Psychiatry Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos