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Effect of a novel 5‐HT 3 receptor agonist MKC‐733 on upper gastrointestinal motility in humans
Author(s) -
Coleman N. S.,
Marciani L.,
Blackshaw E.,
Wright J.,
Parker M.,
Yano T.,
Yamazaki S.,
Chan P. Q.,
Wilde K.,
Gowland P. A.,
Perkins A. C.,
Spiller R. C.
Publication year - 2003
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1046/j.1365-2036.2003.01797.x
Subject(s) - gastric emptying , antrum , medicine , migrating motor complex , stomach , gastroenterology , agonist , duodenum , motility , magnetic resonance imaging , endocrinology , receptor , biology , radiology , genetics
Summary Background : Although 5‐HT 3 antagonists have been used to treat chemotherapy‐induced emesis and diarrhoea‐predominant irritable bowel syndrome, the effects of 5‐HT 3 agonists in humans are unknown. Aim : To determine the effect of MKC‐733, a selective 5‐HT 3 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.