Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation- predominant irritable bowel syndrome? A randomized controlled trial

A. E. Foxx-Orenstein, Michael Camilleri, Lawrence Szarka, S. Mckinzie, D. Burton, G. Thomforde, K. Baxter, A. R. Zinsmeister

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Opioid neurons exhibit tonic restraint on intestinal motility; opioid antagonists stimulate peristalsis and increase transit. In vitro, 5-hydroxytryptamine (5-HT4) agonists combined with selective opioid antagonists significantly increased colonic propulsion relative to a 5-HT 4 agonist alone. We hypothesized that the combination of 5-HT 4 agonist and non-selective opioid antagonist enhances intestinal transit more than either treatment alone in female constipation-predominant irritable bowel syndrome (C-IBS) patients. Our aim was to examine the effect of tegaserod 6 mg b.i.d. alone and combined with naltrexone 50 mg on intestinal transit and stool characteristics in females with C-IBS. Forty-eight patients were randomized to tegaserod alone, naltrexone alone or in combination with tegaserod or placebo for 6 days. Small bowel, ascending colon half-life (in pharmacokinetics) (t1/2), and colonic geometric centre (8, 24, 48 h) were assessed by scintigraphy. Tegaserod increased small bowel (P < 0.01) and colon transit (P < 0.01). Naltrexone did not accelerate colonic transit relative to placebo. Combination treatment did not significantly accelerate transit relative to tegaserod alone. Tegaserod and tegaserod with naltrexone resulted in looser stool form (P < 0.01). In female C-IBS patients, tegaserod accelerates small bowel and colon transit and contributed to looser stool consistency. Use of naltrexone, 50 mg, does not support the hypothesis that combination of 5-HT4 agonist and non-selective opioid antagonist enhances intestinal transit.

Original languageEnglish (US)
Pages (from-to)821-830
Number of pages10
JournalNeurogastroenterology and Motility
Volume19
Issue number10
DOIs
StatePublished - Oct 2007

Fingerprint

Opiate Alkaloids
Serotonin 5-HT4 Receptor Agonists
Irritable Bowel Syndrome
Constipation
Randomized Controlled Trials
Naltrexone
Narcotic Antagonists
Serotonin Receptor Agonists
Colon
Placebos
Ascending Colon
Peristalsis
Gastrointestinal Motility
tegaserod
Radionuclide Imaging
Opioid Analgesics
Half-Life
Serotonin
Pharmacokinetics

Keywords

  • Constipation-predominant irritable bowel syndrome
  • Naltrexone
  • Serotonin
  • Small intestine
  • Tegaserod
  • Transit

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Does co-administration of a non-selective opiate antagonist enhance acceleration of transit by a 5-HT4 agonist in constipation- predominant irritable bowel syndrome? A randomized controlled trial. / Foxx-Orenstein, A. E.; Camilleri, Michael; Szarka, Lawrence; Mckinzie, S.; Burton, D.; Thomforde, G.; Baxter, K.; Zinsmeister, A. R.

In: Neurogastroenterology and Motility, Vol. 19, No. 10, 10.2007, p. 821-830.

Research output: Contribution to journalArticle

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