ReviewNeurogastroenterology and motility2011
LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin.
Review in Neurogastroenterology and motility, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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
22 citing papers in PubMed, 51 citations in OpenAlex.
- Gut microbiota-mediated berberine metabolism ameliorates cholestatic liver disease by suppressing 5-hydroxytryptamine production.Clinical and molecular hepatology · 2026Trial
- Article
- Serotonergic Control of Gastrointestinal Development, Motility, and Inflammation.Comprehensive Physiology · 2023Article
- Herpes Simplex Virus-1 Induced Serotonin-Associated Metabolic Pathways Correlate With Severity of Virus- and Inflammation-Associated Ocular Disease.Frontiers in microbiology · 2022Article
- Tryptophan-derived serotonin-kynurenine balance in immune activation and intestinal inflammation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Review
- International Union of Basic and Clinical Pharmacology. CX. Classification of Receptors for 5-hydroxytryptamine; Pharmacology and Function.Pharmacological reviews · 2021Review
- Peripartum dietary supplementation of a small-molecule inhibitor of tryptophan hydroxylase 1 compromises infant, but not maternal, bone.American journal of physiology. Endocrinology and metabolism · 2018Article
- New therapeutic perspectives in irritable bowel syndrome: Targeting low-grade inflammation, immuno-neuroendocrine axis, motility, secretion and beyond.World journal of gastroenterology · 2017Review
- PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease.JCI insight · 2016Article
- Alterations in serotonin, transient receptor potential channels and protease-activated receptors in rats with irritable bowel syndrome attenuated by Shugan decoction.World journal of gastroenterology · 2015Article
- Adult Tph2 knockout mice without brain serotonin have moderately elevated spine trabecular bone but moderately low cortical bone thickness.BoneKEy reports · 2015Article
- Pilot study of Biomarkers for predicting effectiveness of ramosetron in diarrhea-predominant irritable bowel syndrome: expression of S100A10 and polymorphisms of TPH1.Neurogastroenterology and motility · 2015Article
- Recent advances in pharmacological treatment of irritable bowel syndrome.World journal of gastroenterology · 2014Review
- TPH gene polymorphisms are associated with disease perception and quality of life in women with irritable bowel syndrome.Biological research for nursing · 2014Article
- Identification of a functional TPH1 polymorphism associated with irritable bowel syndrome bowel habit subtypes.The American journal of gastroenterology · 2013Article
- Combination of carbonic anhydrase inhibitor, acetazolamide, and sulforaphane, reduces the viability and growth of bronchial carcinoid cell lines.BMC cancer · 2013Article
- Serotonin signalling in the gut--functions, dysfunctions and therapeutic targets.Nature reviews. Gastroenterology & hepatology · 2013Review
- Molecular dynamics simulation of tryptophan hydroxylase-1: binding modes and free energy analysis to phenylalanine derivative inhibitors.International journal of molecular sciences · 2013Article
- New treatments for IBS.Nature reviews. Gastroenterology & hepatology · 2013Review
- Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome.American journal of physiology. Gastrointestinal and liver physiology · 2012Review
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
LX-1031 is an oral, small molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces serotonin (5-HT) synthesis peripherally. It has potential for illnesses characterized by excess 5-HT, such as diarrhea-predominant irritable bowel syndrome (IBS-D) and carcinoid diarrhea. In vitro, inhibition of TPH1 occurred in 10(-8) -10(-7) mol L(-1) range. In vivo in rodents, LX-1031 has no effect on brain 5-HT while dose-dependently reducing 5-HT, particularly in the small bowel. After oral LX1031 in humans, systemic exposure is very low, plasma concentrations are linear in dose range 250-750 mg q.i.d.; the median T(1/2) for elimination is ∼ 20 h, and repeat administration for 14 days doubles C(max) . In ascending-single-dose and multiple-dose (14 days) trials in healthy volunteers, LX-1031, 2-4 g day(-1) significantly reduced urinary 5-hydroxyindoleacetic acid (5-HIAA) starting by Day 5, and persisting over the 14 day exposure. There are no dose-limiting toxicities in healthy subjects or remarkable adverse effects in clinical trials to date. Over a 28-day treatment period, LX-1031 was associated with improved weekly global scores (2/4 weeks) and improved stool consistency with lower urinary 5-HIAA excretion. LX-1031 appears promising for chronic diarrhea associated with increased 5-HT expression including IBS-D. Optimal doses, efficacy and safety in IBS clinical trials need to be fully elucidated; low systemic exposure, selectivity for TPH1 over TPH2, and lack of effect on brain 5-HT in several species suggest that LX-1031 is unlikely to cause affective disorders.
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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.