ArticleProceedings of the National Academy of Sciences of the United States of America2013
Ligands that interact with putative MOR-mGluR5 heteromer in mice with inflammatory pain produce potent antinociception.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 86 citations in OpenAlex.
- Metabotropic Glutamate Receptor 5: A Potential Target for Neuropathic Pain Treatment.Current neuropharmacology · 2025Review
- The crosstalk between 5-HTNeuropharmacology · 2023Review
- MMG22 Potently Blocks Hyperalgesia in Cisplatin-treated Mice.Neuroscience · 2023Article
- The opioid receptor: emergence through millennia of pharmaceutical sciences.Frontiers in pain research (Lausanne, Switzerland) · 2023Review
- Analgesic efficacy of sleep-promoting pharmacotherapy in patients with chronic pain: a systematic review and meta-analysis.Pain reports · 2023Review
- Oligomerization of the heteromeric γ-aminobutyric acid receptor GABAScientific reports · 2022Article
- Novel bivalent ligands carrying potential antinociceptive effects by targeting putative mu opioid receptor and chemokine receptor CXCR4 heterodimers.Bioorganic chemistry · 2022Article
- Artesunate Alleviates Paclitaxel-Induced Neuropathic Pain in Mice by Decreasing Metabotropic Glutamate Receptor 5 Activity and Neuroinflammation in Primary Sensory Neurons.Frontiers in molecular neuroscience · 2022Article
- Structural Characterization of Receptor-Receptor Interactions in the Allosteric Modulation of G Protein-Coupled Receptor (GPCR) Dimers.International journal of molecular sciences · 2021Review
- Allosteric Interactions between Adenosine AInternational journal of molecular sciences · 2021Review
- Structural and Biophysical Mechanisms of Class C G Protein-Coupled Receptor Function.Trends in biochemical sciences · 2020Review
- Multifunctional Opioid-Derived Hybrids in Neuropathic Pain: Preclinical Evidence, Ideas and Challenges.Molecules (Basel, Switzerland) · 2020Review
- Bivalent Ligand Aiming Putative Mu Opioid Receptor and Chemokine Receptor CXCR4 Dimers in Opioid Enhanced HIV-1 Entry.ACS medicinal chemistry letters · 2020Article
- Article
- Activation of µ-δ opioid receptor heteromers inhibits neuropathic pain behavior in rodents.Pain · 2020Article
- Targeting MOR-mGluRNeuropharmacology · 2019Article
- The bivalent ligand MCC22 potently attenuates hyperalgesia in a mouse model of cisplatin-evoked neuropathic pain without tolerance or reward.Neuropharmacology · 2019Article
- Current strategies toward safer mu opioid receptor drugs for pain management.Expert opinion on therapeutic targets · 2019Review
- The Endocannabinoid System as a Target in Cancer Diseases: Are We There Yet?Frontiers in pharmacology · 2019Review
- A bivalent compound targeting CCR5 and the mu opioid receptor treats inflammatory arthritis pain in mice without inducing pharmacologic tolerance.Arthritis research & therapy · 2018Article
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6 authors at 1 institution in 1 country.
Funding
Abstract
The low effectiveness of morphine and related mu opioid analgesics for the treatment of chronic inflammatory pain is a result of opioid-induced release of proinflammatory cytokines and glutamate that lower the pain threshold. In this regard, the use of opioids with metabotropic glutamate-5 receptor (mGluR5) antagonist has been reported to increase the efficacy of morphine and prevent the establishment of adverse effects during chronic use. Given the presence of opioid receptors (MORs) and mGluR5 in glia and neurons, together with reports that suggest coexpressed MOR/mGluR5 receptors in cultured cells associate as a heteromer, the possibility that such a heteromer could be a target in vivo was addressed by the design and synthesis of a series of bivalent ligands that contain mu opioid agonist and mGluR5 antagonist pharmacophores linked through spacers of varying length (10-24 atoms). The series was evaluated for antinociception using the tail-flick and von Frey assays in mice pretreated with lipopolysaccharide (LPS) or in mice with bone cancer. In LPS-pretreated mice, MMG22 (4c, 22-atom spacer) was the most potent member of the series (intrathecal ED50 ∼9 fmol per mouse), whereas in untreated mice its ED50 was more than three orders of magnitude higher. As members of the series with shorter or longer spacers have ≥500-fold higher ED50s in LPS-treated mice, the exceptional potency of MMG22 may be a result of the optimal bridging of protomers in a putative MOR-mGluR5 heteromer. The finding that MMG22 possesses a >10(6) therapeutic ratio suggests that it may be an excellent candidate for treatment of chronic, intractable pain via spinal administration.
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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.