title: Effect of a novel 5-HT3 receptor agonist MKC-733 on upper gastrointestinal motility in humans.
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.
  
  
  OBJECTIVE
  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.
authors: Division of Gastroenterology, School of Medical and Surgical Sciences, University Hospital, Nottingham, UK.
authors: N S
authors: NS
authors: Coleman
authors: L
authors: L
authors: Marciani
authors: E
authors: E
authors: Blackshaw
authors: J
authors: J
authors: Wright
authors: M
authors: M
authors: Parker
authors: T
authors: T
authors: Yano
authors: S
authors: S
authors: Yamazaki
authors: P Q
authors: PQ
authors: Chan
authors: K
authors: K
authors: Wilde
authors: P A
authors: PA
authors: Gowland
authors: A C
authors: AC
authors: Perkins
authors: R C
authors: RC
authors: Spiller
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D018592:Cross-Over Studies; D004311:Double-Blind Method; D015902:Gamma Cameras; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008365:Manometry; D008875:Middle Aged; D011725:Pyridines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D011877:Radionuclide Imaging; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D013270:Stomach / Q000000981:diagnostic imaging
chemical_list: D011725:Pyridines; D011812:Quinuclidines; D058827:Serotonin 5-HT3 Receptor Agonists; D017366:Serotonin Receptor Agonists; C482040:Pumosetrag