ArticleThe Journal of biological chemistry2014
Blocking metabotropic glutamate receptor subtype 7 (mGlu7) via the Venus flytrap domain (VFTD) inhibits amygdala plasticity, stress, and anxiety-related behavior.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 74 citations in OpenAlex.
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- Negative allosteric modulator of the metabotropic glutamate receptor 7 ADX71743 increases wakefulness, reduces sleep, and alters stress-induced changes in the brain neurotransmitter levels.The international journal of neuropsychopharmacology · 2026Article
- Profiling metabotropic glutamate receptor 7 expression in Rett syndrome: consequences for pharmacotherapy.Neuroscience · 2026Article
- Negative allosteric modulation of mGlu7 disrupts fear memory reconsolidation and glutamatergic signaling in rat and human brain tissue.Molecular psychiatry · 2026Article
- Overexpression of mGluMolecular neurobiology · 2025Article
- Profiling the Impact of mGluACS chemical neuroscience · 2025Article
- Role of mGluR7 in Alzheimer's disease: pathophysiological insights and therapeutic approaches.Inflammopharmacology · 2025Review
- mGlu4R, mGlu7R, and mGlu8R allosteric modulation for treating acute and chronic neurodegenerative disorders.Pharmacological reports : PR · 2024Review
- Promiscuous involvement of metabotropic glutamate receptors in the storage ofPhilosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Therapeutic Potential for Metabotropic Glutamate Receptor 7 Modulators in Cognitive Disorders.Molecular pharmacology · 2024Review
- Analysis of single nucleotide polymorphisms of the metabotropic glutamate receptors in a transgender population.Frontiers in endocrinology · 2024Article
- Review
- Differential Activity of Orthosteric Agonists and Allosteric Modulators at Metabotropic Glutamate Receptor 7.Molecular pharmacology · 2023Article
- GRM7 gene mutations and consequences for neurodevelopment.Pharmacology, biochemistry, and behavior · 2023Review
- Design and Synthesis of New Quinazolin-4-one Derivatives with Negative mGluInternational journal of molecular sciences · 2023Article
- Development and profiling of mGluBioorganic & medicinal chemistry letters · 2022Article
- Allosteric Modulators of Metabotropic Glutamate Receptors as Novel Therapeutics for Neuropsychiatric Disease.Pharmacological reviews · 2022Review
- Article
- A large consanguineous family with a homozygous Metabotropic Glutamate Receptor 7 (mGlu7) variant and developmental epileptic encephalopathy: Effect on protein structure and ligand affinity.Orphanet journal of rare diseases · 2021Article
- Allosteric Molecular Switches in Metabotropic Glutamate Receptors.ChemMedChem · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The metabotropic glutamate receptor subtype 7 (mGlu7) is an important presynaptic regulator of neurotransmission in the mammalian CNS. mGlu7 function has been linked to autism, drug abuse, anxiety, and depression. Despite this, it has been difficult to develop specific blockers of native mGlu7 signaling in relevant brain areas such as amygdala and limbic cortex. Here, we present the mGlu7-selective antagonist 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one (XAP044), which inhibits lateral amygdala long term potentiation (LTP) in brain slices from wild type mice with a half-maximal blockade at 88 nm. There was no effect of XAP044 on LTP of mGlu7-deficient mice, indicating that this pharmacological effect is mGlu7-dependent. Unexpectedly and in contrast to all previous mGlu7-selective drugs, XAP044 does not act via the seven-transmembrane region but rather via a binding pocket localized in mGlu7's extracellular Venus flytrap domain, a region generally known for orthosteric agonist binding. This was shown by chimeric receptor studies in recombinant cell line assays. XAP044 demonstrates good brain exposure and wide spectrum anti-stress and antidepressant- and anxiolytic-like efficacy in rodent behavioral paradigms. XAP044 reduces freezing during acquisition of Pavlovian fear and reduces innate anxiety, which is consistent with the phenotypes of mGlu7-deficient mice, the results of mGlu7 siRNA knockdown studies, and the inhibition of amygdala LTP by XAP044. Thus, we present an mGlu7 antagonist with a novel molecular mode of pharmacological action, providing significant application potential in psychiatry. Modeling the selective interaction between XAP044 and mGlu7's Venus flytrap domain, whose three-dimensional structure is already known, will facilitate future drug development supported by computer-assisted drug design.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.