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Related Concept Videos

Drugs for Treatment of Diarrhea-Predominant IBS01:17

Drugs for Treatment of Diarrhea-Predominant IBS

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Diarrhea-predominant irritable bowel syndrome (IBS-D) is a subtype of IBS characterized primarily by frequent, loose, or watery stools, abdominal pain, and abdominal discomfort. Therapeutic approaches to managing IBS-D include dietary changes, stress management techniques, and pharmaceutical interventions.
Two specific drugs used in the treatment are alosetron (Lotronex) and eluxadoline (Viberzi). Alosetron, a 5-HT3 antagonist, works by slowing the movement of stools in the gut, reducing bowel...
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Drugs Affecting GI Tract Motility: Serotonin Receptor Agonists01:23

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Serotonin, a crucial neurotransmitter synthesized by enterochromaffin cells, plays a cardinal role in regulating gastrointestinal (GI) motility. With over 90% of the body's total serotonin in the GI tract, its influence on digestive processes is profound. Serotonin is swiftly released upon various stimuli, such as food boluses or certain drugs, triggering intrinsic sensory neurons in the myenteric plexus and extrinsic vagal and spinal sensory neurons. This leads to the activation of the...
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Drugs for Treatment of Constipation-Predominant IBS01:21

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Pharmacological therapies for IBS-C are designed to alleviate abdominal discomfort and enhance bowel function. In patients with IBS-C, fiber supplements may help soften stools and decrease straining, but may also lead to increased gas production and bloating. Osmotic laxatives like milk of magnesia are frequently used to soften stools and increase stool frequency in IBS-C patients. In addition, two drugs approved for use in severe IBS-C adult cases are linaclotide (Linzess) and lubiprostone...
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Glucagon-like Receptor Agonists01:24

Glucagon-like Receptor Agonists

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Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
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Inflammatory Bowel Disease IV: Pharmacological Management01:29

Inflammatory Bowel Disease IV: Pharmacological Management

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Upon diagnosis, managing Inflammatory Bowel Disease (IBD) involves addressing several crucial aspects. The primary goals include resting the bowel, correcting malnutrition, and providing symptomatic relief. Resting the bowel may consist of medications to reduce inflammation and promote healing. Correcting malnutrition is essential, often requiring dietary adjustments and nutritional supplements. Symptomatic relief aims to ease pain, diarrhea, and other discomforts in IBD.
Pharmacologic...
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Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists01:28

Drugs Affecting GI Tract Motility: Dopamine Receptor Antagonists

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Prokinetic agents are specialized medications that stimulate gastrointestinal (GI) motility, promoting food movement through the GI tract. Dopamine, an inhibitory neurotransmitter, plays a significant role in this process, reducing GI motility and indirectly controlling the speed of digestion. Dopamine receptor antagonists, such as metoclopramide and domperidone, offer a unique advantage as prokinetic agents. By blocking the dopamine receptors, these drugs increase GI motility, improving food...
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Related Experiment Video

Updated: Feb 28, 2026

Real Time Monitoring of Intracellular Bile Acid Dynamics Using a Genetically Encoded FRET-based Bile Acid Sensor
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A novel intestinal-restricted FXR agonist.

Hong Wang1, Zhou Zhao1, Jiyu Zhou1

  • 1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Tongjiaxiang#24, Nanjing 210009, China; Key Lab of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Tongjiaxiang#24, Nanjing 210009, China.

Bioorganic & Medicinal Chemistry Letters
|June 21, 2017
PubMed
Summary

A novel intestinal-restricted FXR agonist, fexaramine-3 (Fex-3), selectively activates the target receptor in the ileum. This new compound demonstrates superior efficacy over fexaramine (Fex) in modulating bile acid synthesis pathways.

Keywords:
AgonistFarnesoid X receptorFexaramineIntestinal-restricted

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Ileectomy-induced Bile Overaccumulation in Mouse Intestine
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Forskolin-induced Swelling in Intestinal Organoids: An In Vitro Assay for Assessing Drug Response in Cystic Fibrosis Patients
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Ileectomy-induced Bile Overaccumulation in Mouse Intestine
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Ileectomy-induced Bile Overaccumulation in Mouse Intestine

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Area of Science:

  • Pharmacology
  • Hepatology
  • Gastroenterology

Background:

  • Bile acid synthesis is regulated by the Farnesoid X receptor (FXR).
  • Intestinal FXR agonists offer therapeutic potential for metabolic and liver diseases.
  • Existing FXR agonists may lack sufficient selectivity or exhibit off-target effects.

Purpose of the Study:

  • To develop and characterize a novel intestinal-restricted FXR agonist, fexaramine-3 (Fex-3).
  • To compare the efficacy and selectivity of Fex-3 against a known FXR agonist, fexaramine (Fex).
  • To investigate the potential of Fex-3 in modulating bile acid homeostasis and its application in obesity treatment.

Main Methods:

  • In vitro assays to assess FXR activation and target gene expression.
  • In vivo studies in animal models to evaluate pharmacological effects.
  • Quantitative analysis of gene expression (BSEP, SHP, CYP7A1) and FXR binding in the ileum.

Main Results:

  • Fex-3 selectively activated intestinal FXR, particularly in the ileum.
  • Fex-3 demonstrated superior induction of BSEP and SHP expression compared to Fex.
  • Fex-3 exhibited enhanced suppression of CYP7A1, a key enzyme in bile acid synthesis, relative to Fex.
  • Fex-3 showed improved selectivity for intestinal FXR compared to Fex.

Conclusions:

  • Fex-3 represents a promising new intestinal-restricted FXR agonist with enhanced selectivity and efficacy.
  • Fex-3 effectively modulates bile acid synthesis pathways by targeting ileal FXR.
  • Further research into Fex-3 for obesity treatment is warranted.