Trial reportPsychopharmacology2018
Group II metabotropic glutamate receptor agonist prodrugs LY2979165 and LY2140023 attenuate the functional imaging response to ketamine in healthy subjects.
Trial report in Psychopharmacology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
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Who cites it
22 citing papers in PubMed, 49 citations in OpenAlex.
- Effect of mGluR2 positive allosteric modulation on frontostriatal working memory activation in schizophrenia.Molecular psychiatry · 2022Trial
- Proof of mechanism and target engagement of glutamatergic drugs for the treatment of schizophrenia: RCTs of pomaglumetad and TS-134 on ketamine-induced psychotic symptoms and pharmacoBOLD in healthy volunteers.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2020Trial
- Ketamine effects on default mode network activity and vigilance: A randomized, placebo-controlled crossover simultaneous fMRI/EEG study.Human brain mapping · 2020Trial
- Pharmacological MRI: Utility in Understanding Drug Mechanisms in Psychiatric Disorders.Journal of magnetic resonance imaging : JMRI · 2026Review
- Review
- Corticolimbic circuitry as a druggable target in schizophrenia spectrum disorders: a narrative review.Translational psychiatry · 2025Review
- Finding the Right Dose: NMDA Receptor-Modulating Treatments for Cognitive and Plasticity Deficits in Schizophrenia and the Role of Pharmacodynamic Target Engagement.Biological psychiatry · 2025Review
- Effectiveness of positive allosteric modulators of metabotropic glutamate receptor 2/3 (mGluR2/3) in animal models of schizophrenia.Translational psychiatry · 2025Review
- Visual mismatch negativity in Parkinson's psychosis and potential for testing treatment mechanisms.Brain communications · 2024Article
- The mGluRNaunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Effects of the mGlu2/3 receptor agonist LY379268 on two models of disturbed auditory evoked brain oscillations in mice.Translational psychiatry · 2023Article
- Opposite Modulation of the NMDA Receptor by Glycine and S-Ketamine and the Effects on Resting State EEG Gamma Activity: New Insights into the Glutamate Hypothesis of Schizophrenia.International journal of molecular sciences · 2023Article
- Progress and Pitfalls in Developing Agents to Treat Neurocognitive Deficits Associated with Schizophrenia.CNS drugs · 2022Review
- Control of impulsivity by GCommunications biology · 2021Article
- The M1/M4 preferring muscarinic agonist xanomeline modulates functional connectivity and NMDAR antagonist-induced changes in the mouse brain.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2021Article
- Safety and pharmacokinetic profiles of MGS0274 besylate (TS-134), a novel metabotropic glutamate 2/3 receptor agonist prodrug, in healthy subjects.British journal of clinical pharmacology · 2020Article
- Targeting Serotonin 5-HTCNS drugs · 2020Review
- The NIMH 'Fast-Fail Trials' (FAST) Initiative: Rationale, Promise, and Progress.Pharmaceutical medicine · 2020Review
- Review
- Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.Frontiers in pharmacology · 2020Review
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAberrant glutamate neurotransmission, and in particular dysfunction of the N-methyl-D-aspartate receptor (NMDAR), has been implicated in psychiatric disorders and represents a novel therapeutic target. Low-dose administration of the NMDA antagonist ketamine in healthy volunteers elicits a strong blood oxygenation level dependent (BOLD) imaging signal that can be attenuated by pretreatment with single, therapeutically effective doses of marketed medicines interacting with the glutamate system.
objectiveTo test the attenuation of the ketamine-induced BOLD signal by pretreatment with either a metabotropic glutamate receptor (mGluR) 2/3 or a mGluR2 agonist in healthy volunteers
methodsWe used a ketamine challenge pharmacological magnetic resonance imaging (phMRI) paradigm to assess the modulatory effects of single acute doses of LY2140023 (pomaglumetad methionil), the methionine prodrug of the mGluR2/3 agonist LY404039 (10, 40, and 160 mg; N = 16 subjects) and of LY2979165, and the alanine prodrug of the selective orthosteric mGluR2 agonist 2812223 (20 and 60 mg; N = 16 subjects).
resultsA reduction in the ketamine-evoked BOLD phMRI signal relative to placebo was observed at the highest doses tested of both LY2140023 and LY2979165. A relationship was observed between reduction of the BOLD signal and increasing plasma levels of 2812223 in the LY2979165 cohort.
conclusionsThese results identify pharmacologically active doses of the group II mGluR agonist prodrugs LY2140023 and LY2979165 in humans. They also extend the classes of compounds that have been experimentally shown to reverse the ketamine-evoked phMRI signal in humans, further supporting the use of this method as a neuroimaging biomarker for assessing functional effects.
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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.