ArticleAnnals of clinical and translational neurology2016
Metabotropic glutamate receptor 5: a target for migraine therapy.
Article in Annals of clinical and translational neurology, 2016. 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 trial behind it
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Who cites it
22 citing papers in PubMed, 43 citations in OpenAlex.
- The therapeutic pipeline in migraine: What does the future hold?Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Review
- Emerging pharmacological targets in migraine therapy: CGRP and beyond.Frontiers in pharmacology · 2026Review
- Glutamate as a Therapeutic Substrate in Migraine.International journal of molecular sciences · 2025Review
- The Potential Role of Glutamate Receptors and their Antagonists or Modulators in Migraine Therapy.Current neuropharmacology · 2025Review
- Insights into the Metabolism, Disposition, and Quantitative Profile of mGlu5 NAM AE90015 with Metabolite Identification and a Novel Integration Method.Molecules (Basel, Switzerland) · 2024Article
- Enhanced mGluRCell death & disease · 2024Article
- Targeting Glutamate Neurotoxicity through Dietary Manipulation: Potential Treatment for Migraine.Nutrients · 2023Review
- Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations.International journal of molecular sciences · 2023Review
- Migraine: from pathophysiology to treatment.Journal of neurology · 2023Review
- Targeting Peripheral N-Methyl-D-Aspartate Receptor (NMDAR): A Novel Strategy for the Treatment of Migraine.Journal of clinical medicine · 2023Review
- New Oral Drugs for Migraine.CNS drugs · 2022Review
- Reducing the Burden of Migraine: Safety and Efficacy of CGRP Pathway-Targeted Preventive Treatments.Journal of clinical medicine · 2022Review
- Light-Induced Activation of a Specific Type-5 Metabotropic Glutamate Receptor Antagonist in the Ventrobasal Thalamus Causes Analgesia in a Mouse Model of Breakthrough Cancer Pain.International journal of molecular sciences · 2022Article
- Kynurenine Pathway of Tryptophan Metabolism in Migraine and Functional Gastrointestinal Disorders.International journal of molecular sciences · 2021Review
- Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period.The journal of headache and pain · 2021Article
- Pathophysiological Mechanisms in Migraine and the Identification of New Therapeutic Targets.CNS drugs · 2019Review
- Computational Drug Design Applied to the Study of Metabotropic Glutamate Receptors.Molecules (Basel, Switzerland) · 2019Review
- Glutamate and Its Receptors as Therapeutic Targets for Migraine.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2018Review
- Recent Advances in Pharmacotherapy for Migraine Prevention: From Pathophysiology to New Drugs.Drugs · 2018Review
- An update on migraine: current understanding and future directions.Journal of neurology · 2017Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
introductionMany patients suffering from migraine gain little relief from existing treatments partly because many existing acute and preventive therapies used in migraine have been adopted from other neurologic conditions such as depression or epilepsy. Here, we present data supporting a new migraine-specific target, the mGlu5 receptor.
methodsWe studied the effect of mGlu5 blockade using ADX10059, on neuronal firing in the trigeminocervical complex (TCC) and durovascular effects of nociceptive trigeminovascular activation in the anesthetized rat. The clinical potential of the mGlu5 mechanism was tested with ADX10059 orally in a double-blind placebo-controlled, parallel group, clinical trial.
resultsThe negative allosteric mGlu5 modulator ADX10059 attenuated dural vasodilator responses to meningeal stimulation in a dose-dependent manner, comparable to naratriptan, while the N-methyl-d-aspartate receptor blocker MK-801 had no effect. ADX10059 reduced responses of trigeminocervical neurons to dural stimulation, most strikingly affecting their spontaneous firing rate. Immunostaining identified mGlu5 and not mGlu1a receptors in the TCC. The primary efficacy endpoint for the clinical trial, 2 h pain free, demonstrated a significant effect of ADX10059 375 mg, 17%, versus placebo, 5%. No serious adverse events were reported at the primary dose, with transient dizziness being the most common treatment-emergent event at 48%.
interpretationOur findings provide preclinical and clinical proof of concept establishing mGlu5 as a novel therapeutic target in the treatment of migraine. Although ADX10059 is unsuitable as a therapeutic candidate, because of hepatoxicity detected in a subsequent study, the data open a new direction for migraine research and therapy.
Identifiers
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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.