ArticleBiochemical pharmacology2014
Molecular characterization of eluxadoline as a potential ligand targeting mu-delta opioid receptor heteromers.
Article in Biochemical pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 76 citations in OpenAlex.
- Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist.The Journal of pharmacology and experimental therapeutics · 2016Trial
- Effect of uptake transporters OAT3 and OATP1B1 and efflux transporter MRP2 on the pharmacokinetics of eluxadoline.Journal of clinical pharmacology · 2015Trial
- The Orexin System in Addiction: Neuromodulatory Interactions and Therapeutic Potential.Brain sciences · 2025Review
- Chronic Visceral Pain: New Peripheral Mechanistic Insights and Resulting Treatments.Gastroenterology · 2024Review
- Single-dose Pharmacokinetics of Eluxadoline in Healthy Participants With Normal Renal Function and Participants With Renal Impairment.Clinical pharmacology in drug development · 2023Article
- An Open-Label Study to Evaluate the Effect of Eluxadoline on the Single-Dose Pharmacokinetics of Midazolam in Healthy Participants.Clinical pharmacology in drug development · 2022Article
- GPCR heteromers: An overview of their classification, function and physiological relevance.Frontiers in endocrinology · 2022Review
- Use of home cage wheel running to assess the behavioural effects of administering a mu/delta opioid receptor heterodimer antagonist for spontaneous morphine withdrawal in the rat.Behavioural brain research · 2021Article
- Post-marketing reports of pancreatitis in eluxadoline-treated patients pre and post US label change.Therapeutic advances in gastroenterology · 2021Article
- Mu and Delta Opioid Receptors Are Coexpressed and Functionally Interact in the Enteric Nervous System of the Mouse Colon.Cellular and molecular gastroenterology and hepatology · 2020Article
- The Active Ingredients Identification and Antidiarrheal Mechanism Analysis ofFrontiers in pharmacology · 2020Article
- The Possible Role of MOPr-DOPr Heteromers and Its Regulatory Protein RTP4 at Sensory Neurons in Relation to Pain Perception.Frontiers in cellular neuroscience · 2020Review
- Paradoxical Pain from Opioids: Increased Risk of Acute Pancreatitis.Digestive diseases and sciences · 2020Article
- G-Protein-Coupled Receptors Are Dynamic Regulators of Digestion and Targets for Digestive Diseases.Gastroenterology · 2019Review
- Current strategies toward safer mu opioid receptor drugs for pain management.Expert opinion on therapeutic targets · 2019Review
- Regulation of an Opioid Receptor Chaperone Protein, RTP4, by Morphine.Molecular pharmacology · 2019Article
- Psychotropics, Antidepressants, and Visceral Analgesics in Functional Gastrointestinal Disorders.Current gastroenterology reports · 2018Review
- Exploring Halogen Bonds in 5-Hydroxytryptamine 2B Receptor-Ligand Interactions.ACS medicinal chemistry letters · 2018Article
- Novel Pharmacological Nonopioid Therapies in Chronic Pain.Current pain and headache reports · 2018Review
- Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System.International journal of molecular sciences · 2018Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Eluxadoline, an orally active mixed μ opioid receptor (μOR) agonist δ opioid receptor (δOR) antagonist developed for the treatment of diarrhea-predominant irritable bowel syndrome, normalizes gastrointestinal (GI) transit and defecation under conditions of novel environment stress or post-inflammatory altered GI function. Furthermore, compared to loperamide, which is used to treat non-specific diarrhea, the effects of eluxadoline on GI transit occur over a wider dosage range. However, the mechanisms of action of eluxadoline are unclear. In this study, we compared the ability of eluxadoline and loperamide to activate G-protein- and β-arrestin-mediated signaling at μOR homomers or μOR-δOR heteromers in heterologous cells. We also examined the ability of both compounds to reduce castor oil induced diarrhea in wild type (WT) and mice lacking δOR. We find that eluxadoline is more potent than loperamide in eliciting G-protein activity and β-arrestin recruitment in μOR expressing cells. However, in cells expressing μOR-δOR heteromers, the potency of eluxadoline is higher, but its maximal effect is lower than that of loperamide. Moreover, in these cells the signaling mediated by eluxadoline but not loperamide is reduced by μOR-δOR heteromer-selective antibodies. We find that in castor oil-induced diarrhea eluxadoline is more efficacious compared to loperamide in WT mice, and δOR appears to play a role in this process. Taken together these results indicate that eluxadoline behaves as a potent μOR agonist in the absence of δOR, while in the presence of δOR eluxadoline's effects are mediated through the μOR-δOR heteromer.
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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.