Basimglurant for treatment of major depressive disorder: a novel negative allosteric modulator of metabotropic glutamate receptor 5

Fuxé, Kjell; Borroto-Escuela, Dasiel O.

doi:10.1517/13543784.2015.1074175

Cited by 34 publications

(21 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The Neuregulin 1 ( NRG1 ) receptor ErbB4, found on GABAergic neurones, has been identified as a potentially druggable target for depression, anxiety and schizophrenia 81 . There is interest in developing agents, such as basimglurant and fenobam, as antidepressants and anxiolytics that target glutamatergic receptors 82 . Estrogen Receptor 2 ( ESR2 ) has previously been implicated in antidepressant action through up-regulation by 3β-hydroxysteroid dehydrogenase 83 .…”

Section: Discussionmentioning

confidence: 99%

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Howard

Adams

Clarke

et al. 2018

Preprint

350

628

View full text Add to dashboard Cite

Major depression is a debilitating psychiatric illness that is typically associated with low mood, anhedonia and a range of comorbidities. Depression has a heritable component that has remained difficult to elucidate with current sample sizes due to the polygenic nature of the disorder. To maximise sample size, we meta-analysed data on 807,553 individuals (246,363 cases and 561,190 controls) from the three largest genome-wide association studies of depression. We identified 102 independent variants, 269 genes, and 15 gene-sets associated with depression, including both genes and gene-pathways associated with synaptic structure and neurotransmission. Further evidence of the importance of prefrontal brain regions in depression was provided by an enrichment analysis. In an independent replication sample of 1,306,354 individuals (414,055 cases and 892,299 controls), 87 of the 102 associated variants were significant following multiple testing correction. Based on the putative genes associated with depression this work also highlights several potential drug repositioning opportunities. These findings advance our understanding of the complex genetic architecture of depression and provide several future avenues for understanding aetiology and developing new treatment approaches.

show abstract

Section: Discussionmentioning

confidence: 99%

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Howard

Adams

Clarke

et al. 2018

Preprint

350

628

View full text Add to dashboard Cite

show abstract

“…The ligand used in this study (ABP-688) is an allosteric modulator, and therefore may not be a valid method of measuring Glu release. Although basimglurant (RO4917523, RG7090), a negative allosteric modulator at the mGlu5R, has shown promise as an adjuvant medication to traditional antidepressant medications (91) in one study, a significant reduction in MADRS was found in the self-reported rather than clinician-administered MADRS and therefore, replication is necessary to support its antidepressant efficacy.…”

Section: Antidepressant Response To Ketamine and Glutamate/gaba Neuromentioning

confidence: 99%

Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

Lener

Niciu

Ballard

et al. 2017

Biological Psychiatry

372

214

View full text Add to dashboard Cite

In patients with major depressive disorder (MDD) or bipolar disorder (BD), abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate (Glu) and gamma-aminobutyric acid (GABA) have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic dose ketamine has led to a collection of studies that have examined neurochemical (e.g. glutamatergic and GABA-ergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation.

show abstract

“…In contrast to such inconsistencies regarding expressional change in mPFC-mGluR5 in the depressive state, it is generally accepted that the administration of an mGluR5 antagonist exerts an anti-depressive effect ( Palucha and Pilc, 2007 ; Pilc et al, 2008 ; Chaki et al, 2013 ; Hashimoto et al, 2013 ; Hughes et al, 2013 ; Fuxe and Borroto-Escuela, 2015 ; Kato et al, 2015 ; Lee K.W. et al, 2015 ; Lindemann et al, 2015 ; Park et al, 2015 ).…”

Section: The Effect Of Mpfc-mglur5 Blockade On the Modulation Of Painmentioning

confidence: 99%

Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression

Chung

Kim

2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Pain and depression affect one another, and this bidirectional interaction implies the existence of common or interacting neural pathways. Among the neural circuits relevant to negative affection, the medial prefrontal cortex (mPFC) is known to be involved in both pain and depression. Persistent stress from physical pain and mental distress can evoke maladaptive changes in mPFC circuits to induce depression. Conversely, the unpleasant mood condition alters mPFC circuits to distort the appraisal of aversion and make individuals vulnerable to pain. In this article, recent findings regarding mPFC in chronic pain and/or depression are reviewed, with particular focus on the metabotropic glutamate receptor 5 (mGluR5). Although the involvement of mGluR5 within the mPFC in both pain and depressive disorders has been extensively studied, there are controversies regarding changes in the activity of the mPFC during chronic pain and depression, and the functional roles of mGluR5 on altered mPFC activity. We discuss alterations in the availability of mGluR5 in the mPFC in these disorders, its role in behavioral manifestations, and its possible influence on cellular subpopulations that mediate dysfunction in the mPFC. We also propose molecular mechanisms that may cause expressional changes in mGluR5 within the mPFC circuitry.

show abstract

Basimglurant for treatment of major depressive disorder: a novel negative allosteric modulator of metabotropic glutamate receptor 5

Cited by 34 publications

References 81 publications

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions

Glutamate and Gamma-Aminobutyric Acid Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine

Metabotropic Glutamate Receptor 5 in the Medial Prefrontal Cortex as a Molecular Determinant of Pain and Ensuing Depression

Contact Info

Product

Resources

About