Effect of MKC-733, a 5-HT3 receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study
Article first published online: 30 NOV 2005
Journal of Clinical Pharmacy and Therapeutics
Volume 30, Issue 6, pages 611–622, December 2005
How to Cite
Fujita, T., Yokota, S., Sawada, M., Majima, M., Ohtani, Y. and Kumagai, Y. (2005), Effect of MKC-733, a 5-HT3 receptor partial agonist, on bowel motility and symptoms in subjects with constipation: an exploratory study. Journal of Clinical Pharmacy and Therapeutics, 30: 611–622. doi: 10.1111/j.1365-2710.2005.00695.x
- Issue published online: 30 NOV 2005
- Article first published online: 30 NOV 2005
- Received 23 September 2004, Accepted 9 February 2005
- a 5-HT3 receptor agonist;
- bowel motility;
- radio-opaque markers
Background: MKC-733, a 5-HT3 receptor partial agonist, is a novel enteroprokinetic compound.
Objective: The aim of this study was to explore the effects of MKC-733 on bowel motility and symptoms in a small group of subjects with constipation. Tolerability was also examined.
Methods: The study was conducted in a single-blind and dose-escalation manner on 14 male and female subjects with constipation aged 22–67 years. After a 1 week run-in period, subjects were treated with placebo (b.i.d.) for 1 week, and 0·2 and 0·5 mg of MKC-733 (b.i.d.) for 2 weeks sequentially. Geometric mean and per cent elimination of surrogate markers of bowel motility were measured by a radio-opaque marker technique at the end of each treatment period. They were analysed on the whole group and subgroups with low (n = 6) and high (n = 8) bowel motility based upon the geometric mean value after placebo treatment. Subjects kept diaries of their bowel habits and gastrointestinal symptoms.
Results: Percent elimination increased after treatment with 0·5 mg MKC-733 compared with placebo treatment in the whole group (70·4 ± 33·5% vs. 47·1 ± 36·6%, mean ± SD, P < 0·05). In the low bowel motility group, both geometric mean and percent elimination increased after treatment with 0·5 mg MKC-733 compared with placebo (7·1 ± 0·9 vs. 5·9 ± 0·5, P < 0·05; 60·0 ± 35·8% vs. 13·3 ± 19·4%, P < 0·05). Stool frequency increased after the first-week treatment with MKC-733 compared with placebo (P < 0·05). Numbers of sensation of incomplete evacuation and gastrointestinal symptoms decreased to half and less after the treatment with MKC-733. No serious adverse effect was noted.
Conclusion: Multiple doses of 0·5 mg MKC-733 improve bowel motility, which was clearly demonstrated in the subjects with decreased bowel motility. MKC-733 at the doses studied might be effective in increasing stool frequency and reduce gastrointestinal symptoms related to constipation. MKC-733 was well tolerated. Further studies will be needed to clarify efficacy and safety of MKC-733 on a larger population.