The effects of ABT‐229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats

Nieuwenhuijs,; Duijvenbode‐Beumer, Van; Verheem,; Visser,; Verhoef,; Gooszen,; Akkermans,

doi:10.1046/j.1365-2362.1999.00364.x

Cited by 22 publications

(8 citation statements)

References 36 publications

(67 reference statements)

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“…Functions of motilin (MLN, P12872) are not usually detected in rodents, although brain and other responses to motilin (MLN, P12872) and the macrolide ABT-229 have been reported and the mechanism of these actions are obscure 1268,1269.…”

Section: Commentsmentioning

confidence: 99%

The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors

Alexander

Benson

Faccenda

et al. 2013

British J Pharmacology

555

336

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The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties of over 2000 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full.G protein-coupled receptors are one of the seven major pharmacological targets into which the Guide is divided, with the others being G protein-coupled receptors, ligand-gated ion channels, ion channels, catalytic receptors, nuclear hormone receptors, transporters and enzymes. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. A new landscape format has easy to use tables comparing related targets.It is a condensed version of material contemporary to late 2013, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in previous Guides to Receptors and Channels. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and the Guide to Receptors and Channels, providing a permanent, citable, point-in-time record that will survive database updates.

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Section: Commentsmentioning

confidence: 99%

The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors

Alexander

Benson

Faccenda

et al. 2013

British J Pharmacology

555

336

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“…This resulted in colonic type bacterial overgrowth in the duodenum, whereas bacterial flora in the ileum was less affected. The proximal small bowel bacterial overgrowth was correlated to bacterial translocation to extraintestinal sites such as the mesenteric lymph nodes, liver and spleen [31]. Likewise, administration of morphine in intensive care patients reduced anteroduodenal motility [27].…”

Section: Bacterial Translocationmentioning

confidence: 99%

“…In Utrecht, several experimental and clinical studies concerning acute pancreatitis, bile duct obstruction and the critically ill have provided insight into the interactions between gastrointestinal motility, bacterial overgrowth, bacterial translocation and infectious complications [21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38,39,40]. Being aware of the continuing controversy and the risks of prophylactic use of antibiotics, research is currently focused on probiotics.…”

Section: Introductionmentioning

confidence: 99%

Prevention of Infectious Complications in Surgical Patients: Potential Role of Probiotics

Besselink

Timmerman²,

Minnen³

et al. 2005

Dig Surg

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Infectious complications in surgical patients often originate from the intestinal microflora. In the critically ill patient, small bowel motility is disturbed, leading to bacterial overgrowth and subsequent bacterial translocation due to dysfunction of the gut mucosal barrier. The optimal prophylactic strategy should act on all these factors, but such a strategy is not yet available. For several decades, antibiotic prophylaxis to prevent translocation of pathogenic bacteria has been studied with conflicting results. Selective decontamination of the digestive tract has shown good results, but fear for bacterial multiresistance has prevented worldwide implementation. In recent years, probiotics, living bacteria with a potential beneficial effect to their host, have shown promising results in several randomized placebo-controlled trials. Currently, in vitro and experimental research focuses on the effects of probiotics on the microflora responsible for gut-derived infections, structural mucosal barrier function and the immune system.

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“…Moreover, the most distinctive symptom of delayed gastric emptying, vomiting, was not included in the symptom complex of these patients. Consistent with this interpretation, the improved symptoms in the non‐obese subgroup appeared to be unrelated to its effect on gastric emptying, 30 further illustrating the complexity between symptom control and the ability to detect quantifiable changes in the rate of gastric emptying. KOS‐2187, another motilide, is effective as a gastroprokinetic in dogs 12 …”

Section: Identifying New Drugs Affecting Gi Motility With Superior Rmentioning

confidence: 54%

“…Progress in motilin receptor research briefly faltered when the motilin receptor agonist and non‐antibiotic motilide ABT‐229, failed to improve symptoms in patients with FD or type 1 diabetes mellitus 29 . However, ABT‐229 is reported to be effective in rats, 30 where functional motilin receptors are thought not to exist; 31 this apparent non‐selectivity of action may in some way explain the potential worsening of symptoms in the clinical trials. Further, in spite of a 20 h plasma half‐life, ABT‐229 was evaluated using a bid dosing regime 29 .…”

Section: Identifying New Drugs Affecting Gi Motility With Superior Rmentioning

confidence: 99%

Development of drugs for gastrointestinal motor disorders: translating science to clinical need

Sanger

Alpers

2008

Neurogastroenterology Motil

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Only a small number of new drugs have recently become available for gastrointestinal (GI) disorders. This is partly because we await outcomes of research into functional bowel disorder aetiology (e.g., role of microbiota) and of trials to control stress- related or painful GI symptoms (e.g., via CRF(1) receptors or beta(3) adrenoceptors). Nevertheless, only the ClC-2 channel activator lubiprostone has recently reached the clinic, joining the 5-HT(3) antagonist alosetron and the long-established 5-HT(4) agonist and D(2) antagonist metoclopramide; tegaserod, a non-selective ligand, was withdrawn. Interestingly, each has shortcomings, providing opportunities for molecules with 5-HT(4) or motilin receptor selectivity, and for new biology via guanylate cyclase C or ghrelin receptor activation. For translation into new drugs, the molecule must have appropriate efficacy, selectivity and pharmacodynamic properties. It is argued that the compound must then be evaluated in conditions where changes in motility are known to exist, before considering more difficult symptomatic conditions such as irritable bowel syndrome (IBS) or functional dyspepsia (FD), where relationships with disordered motility are unclear. Thus, it may be better to begin studying a gastric prokinetic in diabetics requiring improved glucose control, rather than in FD. Notably, new 5-HT(4) receptor agonists are being evaluated firstly as treatments of constipation, not IBS. New antidiarrhoeal agents should be developed similarly. Thus, progression of new drugs may require initial studies in smaller patient populations where clinical outcome is better defined. Only then can disease-related ideas be properly tested and drugs brought forward for these disorders (with high clinical need) and then, if successful for IBS and FD.

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The effects of ABT‐229 and octreotide on interdigestive small bowel motility, bacterial overgrowth and bacterial translocation in rats

Abstract: ABT-229, but not octreotide, reduced morphine induced dysmotility. Small bowel bacterial overgrowth and bacterial translocation were not prevented. Fasting small bowel motility has a regulatory function on the intestinal microflora of the upper small bowel.

Cited by 22 publications

References 36 publications

The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors

The Concise Guide to PHARMACOLOGY 2013/14: G Protein‐Coupled Receptors

Prevention of Infectious Complications in Surgical Patients: Potential Role of Probiotics

Development of drugs for gastrointestinal motor disorders: translating science to clinical need

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