ArticleJournal of medicinal chemistry2014
Putative kappa opioid heteromers as targets for developing analgesics free of adverse effects.
Article in Journal of medicinal chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 35 citations in OpenAlex.
- Intercellular Communication in the Central Nervous System as Deduced by Chemical Neuroanatomy and Quantitative Analysis of Images: Impact on Neuropharmacology.International journal of molecular sciences · 2022Review
- Biased, Bitopic, Opioid-Adrenergic Tethered Compounds May Improve Specificity, Lower Dosage and Enhance Agonist or Antagonist Function with Reduced Risk of Tolerance and Addiction.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Receptor-Receptor Interactions and Glial Cell Functions with a Special Focus on G Protein-Coupled Receptors.International journal of molecular sciences · 2021Review
- Enhancement of Opioid Antinociception by Nicotinic Ligands.The Journal of pharmacology and experimental therapeutics · 2021Article
- Structure-Activity Relationship Studies of 6α- and 6β-Indolylacetamidonaltrexamine Derivatives as Bitopic Mu Opioid Receptor Modulators and Elaboration of the "Message-Address Concept" To Comprehend Their Functional Conversion.ACS chemical neuroscience · 2019Article
- Developing a Biased Unmatched Bivalent Ligand (BUmBL) Design Strategy to Target the GPCR Homodimer Allosteric Signaling (cAMP over β-Arrestin 2 Recruitment) Within the Melanocortin Receptors.Journal of medicinal chemistry · 2019Article
- Receptor-Receptor Interactions as a Widespread Phenomenon: Novel Targets for Drug Development?Frontiers in endocrinology · 2019Review
- Cutting-Edge Search for Safer Opioid Pain Relief: Retrospective Review of Salvinorin A and Its Analogs.Frontiers in psychiatry · 2019Review
- Bivalent ligand MCC22 potently attenuates nociception in a murine model of sickle cell disease.Pain · 2018Article
- Advances in Achieving Opioid Analgesia Without Side Effects.Frontiers in pharmacology · 2018Review
- Novel Molecular Strategies and Targets for Opioid Drug Discovery for the Treatment of Chronic Pain.The Yale journal of biology and medicine · 2017Review
- Contribution of heteromerization to G protein-coupled receptor function.Current opinion in pharmacology · 2017Review
- Dynorphin A analogs for the treatment of chronic neuropathic pain.Future medicinal chemistry · 2016Review
- New paradigms in GPCR drug discovery.Biochemical pharmacology · 2015Review
- Synthesis and characterization of a dual kappa-delta opioid receptor agonist analgesic blocking cocaine reward behavior.ACS chemical neuroscience · 2015Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
It is now generally recognized that upon activation by an agonist, β-arrestin associates with G protein-coupled receptors and acts as a scaffold in creating a diverse signaling network that could lead to adverse effects. As an approach to reducing side effects associated with κ opioid agonists, a series of β-naltrexamides 3-10 was synthesized in an effort to selectively target putative κ opioid heteromers without recruiting β-arrestin upon activation. The most potent derivative 3 (INTA) strongly activated KOR-DOR and KOR-MOR heteromers in HEK293 cells. In vivo studies revealed 3 to produce potent antinociception, which, when taken together with antagonism data, was consistent with the activation of both heteromers. 3 was devoid of tolerance, dependence, and showed no aversive effect in the conditioned place preference assay. As immunofluorescence studies indicated no recruitment of β-arrestin2 to membranes in coexpressed KOR-DOR cells, this study suggests that targeting of specific putative heteromers has the potential to identify leads for analgesics devoid of adverse effects.
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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.