Eluxadoline
[CAS# 864821-90-9]

Identification

• Classification: API >> Other chemicals
• Name: Eluxadoline
• Synonyms: JNJ 27018966
• Molecular Formula: C₃₂H₃₅N₅O₅
• Molecular Weight: 569.65
• CAS Registry Number: 864821-90-9
• EC Number: 811-986-4
• SMILES: CC1=CC(=CC(=C1C[C@@H](C(=O)N(CC2=CC(=C(C=C2)OC)C(=O)O)[C@@H](C)C3=NC=C(N3)C4=CC=CC=C4)N)C)C(=O)N

Properties

• Solubility: Practically insoluble (0.074 g/L) (25 °C), Calc.^*, 10 mM (DMSO) (Expl.)
• Density: 1.284±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.640, Calc.^*
• Boiling Point: 834.2±65.0 °C (760 mmHg), Calc.^*
• Flash Point: 458.3±34.3 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS08 Warning
• Risk Statements: H361
• Safety Statements: P203-P280-P318-P405-P501

Discovery and Applications

Eluxadoline is a pharmacological compound developed primarily for the treatment of irritable bowel syndrome with diarrhea (IBS-D). It is classified as a mixed opioid receptor agonist and antagonist, acting on the mu-opioid receptor and the kappa-opioid receptor. This unique action provides therapeutic benefits in treating IBS-D by modulating gastrointestinal motility and reducing abdominal pain. Eluxadoline is marketed under the brand name Viberzi and is used to alleviate symptoms associated with IBS-D, a condition that affects a significant number of individuals worldwide, leading to discomfort, frequent diarrhea, and other gastrointestinal disturbances.

The discovery of Eluxadoline was rooted in the need for more effective treatments for IBS-D. Previous therapies, including dietary changes, antispasmodic agents, and other medications, did not fully address the complex nature of the disease. Eluxadoline was developed as part of a broader effort to create targeted therapies that directly influence the gastrointestinal system's neuroregulation. By acting on specific opioid receptors, Eluxadoline is able to reduce both the motility of the gut and the perception of pain, offering patients an effective treatment option without the typical opioid-related side effects, such as significant constipation.

The mechanism of action of Eluxadoline involves its dual activity as an agonist at the mu-opioid receptor, which helps in decreasing the motility of the gut, and as an antagonist at the delta-opioid receptor, which is believed to contribute to its analgesic effects. These effects are beneficial in treating the symptoms of IBS-D, as they can reduce the urgency and frequency of diarrhea while also decreasing abdominal discomfort. The pharmacokinetics of Eluxadoline allow it to be taken orally, making it a convenient option for patients.

Eluxadoline is generally well tolerated but may cause side effects, including nausea, constipation, and abdominal pain. It is contraindicated in certain populations, such as those with a history of pancreatitis, severe liver impairment, or a history of biliary duct obstruction. Despite these precautions, Eluxadoline represents a significant advancement in the treatment of IBS-D, providing a much-needed alternative for patients who have not responded well to other therapies.

In addition to its primary application in treating IBS-D, research is ongoing to explore the potential of Eluxadoline for other gastrointestinal disorders and its broader pharmacological effects. By selectively targeting opioid receptors, Eluxadoline exemplifies the potential of targeted therapies in treating complex gastrointestinal conditions, contributing to a more tailored approach in the management of these disorders.

References

2022. Validation of the HPLC-PDA method for detection of eluxadoline and rifaximin in rat plasma and application in a pharmacokinetic study. Future Journal of Pharmaceutical Sciences, 8(1).
DOI: 10.1186/s43094-022-00403-x

2013. Eluxadoline Benefits Patients With Irritable Bowel Syndrome With Diarrhea in a Phase 2 Study. Gastroenterology, 145(2).
DOI: 10.1053/j.gastro.2013.04.006

2012. Identification of a dual δ OR antagonist/μ OR agonist as a potential therapeutic for diarrhea-predominant Irritable Bowel Syndrome (IBS-d). Bioorganic & Medicinal Chemistry Letters, 22(14).
DOI: 10.1016/j.bmcl.2012.05.042