Significant enhancement of esophageal pre-epithelial defense by tegaserod: implications for an esophagoprotective effect.

Abstract

BACKGROUND & AIMS:

Tegaserod, a serotonin 5-hydroxytryptamine (5-HT)4 receptor agonist, is thought to stimulate intestinal secretions. The aim of the current study was to assess the effect of tegaserod vs placebo on salivary and esophageal protective factors in patients with gastroesophageal reflux disease (GERD).

METHODS:

This study was a randomized, double-blind, placebo-controlled, cross-over trial in 38 GERD patients treated with tegaserod 6 mg twice a day vs placebo. Salivary samples were collected basally and during mastication. In addition, in 32 GERD patients, salivary and esophageal secretions also were collected during infusion of NaCl, HCl/pepsin, and NaCl in a consecutive fashion using a specially designed esophageal catheter. Saliva and esophageal perfusates were assessed for the pH, volume, content of buffers, protein, mucin, epidermal growth factor (EGF), transforming growth factor alpha (TGFalpha), and prostaglandin E (PGE)2 and analyzed statistically.

RESULTS:

Salivary flow rates during administration of tegaserod increased over corresponding values during both basal conditions (P < .01) and mastication (P < .001). The rate of secretion of salivary bicarbonate and nonbicarbonate buffers also increased in basal conditions (P < .001 and P < .01, respectively) and during mastication (P < .05 and P = .05). Salivary EGF increased during mastication (P < .05), whereas PGE2 and TGF alpha increased in basal conditions (P < .05 and P < .01). Esophageal perfusate volumes increased during administration of tegaserod in basal conditions (P < .05), whereas esophageal EGF secretion increased after mucosal exposure to HCl/pepsin and subsequent final perfusion with NaCl (P < .05).

CONCLUSIONS:

Significant stimulatory impact of 5-HT4 agonist on several salivary protective factors as well as esophageal EGF secretion may have esophagoprotective implications in patients with GERD and may help to address new therapies in the future.

• Authors: Marek Majewski, Tomasz Jaworski, Irene Sarosiek, Sandra Sostarich, Katherine Roeser, Stanley A Edlavitch, Jeffrey Kralstein, Grzegorz Wallner, Richard W McCallum, Jerzy Sarosiek
• Journal: Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association (Clin Gastroenterol Hepatol) Vol. 5 Issue 4 Pg. 430-8 (Apr 2007) ISSN: 1542-7714 [Electronic] United States
• PMID: 17445751 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Indoles
• Serotonin Receptor Agonists
• tegaserod

Topics

• Administration, Oral
• Adolescent
• Adult
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Double-Blind Method
• Drug Administration Schedule
• Esophageal pH Monitoring
• Esophagoscopy
• Female
• Follow-Up Studies
• Gastric Acidity Determination
• Gastric Mucosa (drug effects)
• Gastroesophageal Reflux (diagnosis, drug therapy)
• Humans
• Indoles (adverse effects, therapeutic use)
• Male
• Middle Aged
• Probability
• Reference Values
• Risk Assessment
• Saliva (chemistry)
• Serotonin Receptor Agonists (adverse effects, therapeutic use)
• Severity of Illness Index
• Treatment Outcome