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Aliment Pharmacol Ther. 2003 Nov 15;18(10):1039-48.

Effect of a novel 5-HT3 receptor agonist MKC-733 on upper gastrointestinal motility in humans.

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  • 1Division of Gastroenterology, School of Medical and Surgical Sciences, University Hospital, Nottingham, UK.

Abstract

BACKGROUND:

Although 5-HT3 antagonists have been used to treat chemotherapy-induced emesis and diarrhoea-predominant irritable bowel syndrome, the effects of 5-HT3 agonists in humans are unknown.

AIM:

To determine the effect of MKC-733, a selective 5-HT3 receptor agonist, on upper gastrointestinal motility.

METHODS:

Oral MKC-733 (0.2, 1 and 4 mg) was compared with placebo in three randomized, double-blind, cross-over studies in healthy males. Antroduodenal manometry was recorded for 8 h during fasting and 3 h post-prandially (n = 12). Gastric emptying and small intestinal transit were determined by gamma-scintigraphy (n = 16). Gastric emptying, accommodation and antral motility were determined by echoplanar magnetic resonance imaging (n = 12).

RESULTS:

MKC-733 (4 mg) increased the number of migrating motor complexes recorded in the antrum and duodenum (P < 0.001), but had no effect on post-prandial motility. MKC-733 delayed scintigraphically assessed liquid gastric emptying (P = 0.005) and accelerated small intestinal transit (P = 0.038). Echoplanar magnetic resonance imaging confirmed the delayed gastric emptying (P < 0.001) and demonstrated a significant increase in cross-sectional area of the proximal stomach (P < 0.01).

CONCLUSIONS:

MKC-733 delays liquid gastric emptying in association with relaxation of the proximal stomach, stimulates fasting antroduodenal migrating motor complex activity and accelerates small intestinal transit.

PMID:
14616171
[PubMed - indexed for MEDLINE]
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