The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS

Tack, Jan; Schumacher, Kai; Tonini, Giulia; Scartoni, Simona; Capriati, Angela; Maggi, Carlo Alberto

doi:10.1136/gutjnl-2015-310683

Cited by 45 publications

(38 citation statements)

References 34 publications

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“…Indeed, antagonists of the tachykinin NK1 and NK2 receptors of substance P and neurokinin A respectively, are being developed for various purposes, among others for symptom relief in IBS. For example, ibodutant, a neurokinin‐2 receptor antagonist, has been shown to improve abdominal pain and stool pattern in female IBS‐D patients . Moreover, neurokinin‐1 receptor antagonists such as aprepitant are currently being used as anti‐emetics and have been suggested as analgesics as well .…”

Section: Discussionmentioning

confidence: 99%

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome

Beckers

Weerts

Helyes

et al. 2017

Aliment Pharmacol Ther

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Section: Discussionmentioning

confidence: 99%

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome

Beckers

Weerts

Helyes

et al. 2017

Aliment Pharmacol Ther

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“…In a phase II, dose-finding study, ibodutant, a highly selective NK2 antagonist with high oral bioavailability, revealed improvement in patients with IBS-D and a baseline pain severity score >1 104. A more recent multinational, double-blind, placebo-controlled study in 559 patients showed dose-dependent improvement of overall symptoms, abdominal pain and stool pattern in IBS-D in females, but not in males, in a phase II, randomised controlled trial; the best efficacy was observed with a 10 mg dose 105. The tolerability of the compound was reported to be excellent.…”

Section: Current Approaches To Manage Visceral Pain In Patients With Ibsmentioning

confidence: 97%

Dietary and pharmacological treatment of abdominal pain in IBS

Camilleri

Boeckxstaens

2017

Gut

127

122

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This review introduces the principles of visceral sensation and appraises the current approaches to management of visceral pain in functional GI diseases, principally IBS. These approaches include dietary measures including fibre supplementation, low fermentable oligosaccharides, disaccharides, monosaccharides and polyols diet, and pharmacological approaches such as antispasmodics, peppermint oil, antidepressants (tricyclic agents, selective serotonin reuptake inhibitors), 5-HT receptor antagonists (alosetron, ondansetron, ramosetron), non-absorbed antibiotic (rifaximin), secretagogues (lubiprostone, linaclotide), μ-opioid receptor (OR) and κ-OR agonist, δ-OR antagonist (eluxadoline), histamine H1 receptor antagonist (ebastine), neurokinin-2 receptor antagonist (ibodutant) and GABAergic agents (gabapentin and pregabalin). Efficacy and safety are discussed based on pivotal trials or published systematic reviews and meta-analysis, expressing ORs or relative risks and their 95% CIs. Potential new approaches may be based on recent insights on mucosal expression of genes, and microRNA and epigenetic markers in human biopsies and in animal models of visceral hypersensitivity.The objectives of this review are to appraise the physiology and anatomy of gut sensation and the efficacy in the relief of visceral pain (typically in IBS) of several classes of therapies. These include fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAPs) and different classes of medications (box 1). Box 1Classes of pharmacological agents for visceral painAntidepressants (tricyclic agents, selective serotonin reuptake inhibitors)Peppermint oil5-HT receptor antagonists (alosetron, ondansetron, ramosetron)Non-absorbed antibiotic (rifaximin)Secretagogues (lubiprostone, linaclotide)μ-Opioid receptor (OR) and κ-OR agonist and δ-OR antagonist (eluxadoline)Histamine H1 receptor antagonist (ebastine)Neurokinin-2 receptor antagonist (ibodutant)GABAergic agents (gabapentin and pregabalin).

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“…[1][2][3] Despite reported heritability in invertebrates 4 and similar evidence from open-field defaecation models in rats, 5 the genetics of stool frequency has not been explored in humans. We undertook a genome-wide association study (GWAS) in two well-characterised population-based cohorts with genotype and defaecation data available: LifeLines-Deep (LLD) from the Netherlands (N=1546; 58% females; mean age 44 years (range 18-86)) and PopCol (PC) from Sweden (N=284; 60% females; mean age 54 years (range 22-71)).…”

mentioning

confidence: 99%

A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency

Jankipersadsing

Hadizadeh

Bonder

et al. 2016

Gut

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The neurokinin-2 receptor antagonist ibodutant improves overall symptoms, abdominal pain and stool pattern in female patients in a phase II study of diarrhoea-predominant IBS

Abstract: NCT01303224.

Cited by 45 publications

References 34 publications

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome

Review article: transient receptor potential channels as possible therapeutic targets in irritable bowel syndrome

Dietary and pharmacological treatment of abdominal pain in IBS

A GWAS meta-analysis suggests roles for xenobiotic metabolism and ion channel activity in the biology of stool frequency

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