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Role of prucalopride, a serotonin (5-HT(4)) receptor agonist, for the treatment of chronic constipation.

Wong BS, Manabe N, Camilleri M - Clin Exp Gastroenterol (2010)

Bottom Line: Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT(4)) agonists have been associated with significant interactions with other receptors (5-HT(1B), 5-HT(1D), and 5-HT(2B) for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market.Prucalopride is a novel gastrointestinal prokinetic agent.It acts as a high affinity, highly-selective 5-HT(4) agonist.

View Article: PubMed Central - PubMed

Affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT
Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT(4)) agonists have been associated with significant interactions with other receptors (5-HT(1B), 5-HT(1D), and 5-HT(2B) for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT(4) agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride's high selectivity for the 5-HT(4) receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments.

No MeSH data available.


Related in: MedlinePlus

Effect of prucalopride on small bowel and colonic transit.Notes: Right panel: Two sets of scintigraphic images obtained from 2 study objects: A) one receiving placebo and B) the other 4 mg of prucalopride. Top images are 4-hour scans and bottom images are 24-hour scans for each individual. Prucalopride accelerates movement of the radioisotope through the colon both at 4 and 24 hours in comparison with placebo. A higher GC value implies more rapid colonic transit, with a value of 4.1 implying that most of the isotope has already been excreted. Left panel: Summary data from groups of patients treated with placebo or prucalopride 2 or 4 mg/day. The histograms show the acceleration of small bowel and ascending colon transit.*P < 0.05 vs placebo treatment..Reprinted from Bouras EP, Camilleri M, Burton DD, et al. Prucalopride accelerates GI and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120:354–360.76Abbreviations: GC, geometric center at 4 (GC 4 h) and 24 (GC 24 h) hours; SBTT, small bowel transit time; AC, ascending colon; pru, prucalopride.
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f1-ceg-3-049: Effect of prucalopride on small bowel and colonic transit.Notes: Right panel: Two sets of scintigraphic images obtained from 2 study objects: A) one receiving placebo and B) the other 4 mg of prucalopride. Top images are 4-hour scans and bottom images are 24-hour scans for each individual. Prucalopride accelerates movement of the radioisotope through the colon both at 4 and 24 hours in comparison with placebo. A higher GC value implies more rapid colonic transit, with a value of 4.1 implying that most of the isotope has already been excreted. Left panel: Summary data from groups of patients treated with placebo or prucalopride 2 or 4 mg/day. The histograms show the acceleration of small bowel and ascending colon transit.*P < 0.05 vs placebo treatment..Reprinted from Bouras EP, Camilleri M, Burton DD, et al. Prucalopride accelerates GI and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120:354–360.76Abbreviations: GC, geometric center at 4 (GC 4 h) and 24 (GC 24 h) hours; SBTT, small bowel transit time; AC, ascending colon; pru, prucalopride.

Mentions: In patients with chronic constipation in whom an evacuation disorder was excluded (Figure 1), prucalopride therapy at 4 mg/day for 1 week42 or at 1 mg/day for 4 weeks43 accelerated gastric emptying half-time,42 ascending colon emptying half-time,42 overall colonic transit,42 orocecal transit time,42,43 and whole gut transit.43 Prucalopride-induced acceleration of colonic transit was also associated with increased stool frequency and loosening of stool consistency in patients with chronic constipation.43,45 Prucalopride exhibited dose responsiveness in effects on gastrointestinal transit and bowel functions.43,44


Role of prucalopride, a serotonin (5-HT(4)) receptor agonist, for the treatment of chronic constipation.

Wong BS, Manabe N, Camilleri M - Clin Exp Gastroenterol (2010)

Effect of prucalopride on small bowel and colonic transit.Notes: Right panel: Two sets of scintigraphic images obtained from 2 study objects: A) one receiving placebo and B) the other 4 mg of prucalopride. Top images are 4-hour scans and bottom images are 24-hour scans for each individual. Prucalopride accelerates movement of the radioisotope through the colon both at 4 and 24 hours in comparison with placebo. A higher GC value implies more rapid colonic transit, with a value of 4.1 implying that most of the isotope has already been excreted. Left panel: Summary data from groups of patients treated with placebo or prucalopride 2 or 4 mg/day. The histograms show the acceleration of small bowel and ascending colon transit.*P < 0.05 vs placebo treatment..Reprinted from Bouras EP, Camilleri M, Burton DD, et al. Prucalopride accelerates GI and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120:354–360.76Abbreviations: GC, geometric center at 4 (GC 4 h) and 24 (GC 24 h) hours; SBTT, small bowel transit time; AC, ascending colon; pru, prucalopride.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3108672&req=5

f1-ceg-3-049: Effect of prucalopride on small bowel and colonic transit.Notes: Right panel: Two sets of scintigraphic images obtained from 2 study objects: A) one receiving placebo and B) the other 4 mg of prucalopride. Top images are 4-hour scans and bottom images are 24-hour scans for each individual. Prucalopride accelerates movement of the radioisotope through the colon both at 4 and 24 hours in comparison with placebo. A higher GC value implies more rapid colonic transit, with a value of 4.1 implying that most of the isotope has already been excreted. Left panel: Summary data from groups of patients treated with placebo or prucalopride 2 or 4 mg/day. The histograms show the acceleration of small bowel and ascending colon transit.*P < 0.05 vs placebo treatment..Reprinted from Bouras EP, Camilleri M, Burton DD, et al. Prucalopride accelerates GI and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120:354–360.76Abbreviations: GC, geometric center at 4 (GC 4 h) and 24 (GC 24 h) hours; SBTT, small bowel transit time; AC, ascending colon; pru, prucalopride.
Mentions: In patients with chronic constipation in whom an evacuation disorder was excluded (Figure 1), prucalopride therapy at 4 mg/day for 1 week42 or at 1 mg/day for 4 weeks43 accelerated gastric emptying half-time,42 ascending colon emptying half-time,42 overall colonic transit,42 orocecal transit time,42,43 and whole gut transit.43 Prucalopride-induced acceleration of colonic transit was also associated with increased stool frequency and loosening of stool consistency in patients with chronic constipation.43,45 Prucalopride exhibited dose responsiveness in effects on gastrointestinal transit and bowel functions.43,44

Bottom Line: Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT(4)) agonists have been associated with significant interactions with other receptors (5-HT(1B), 5-HT(1D), and 5-HT(2B) for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market.Prucalopride is a novel gastrointestinal prokinetic agent.It acts as a high affinity, highly-selective 5-HT(4) agonist.

View Article: PubMed Central - PubMed

Affiliation: Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Mayo Clinic, Rochester, Minnesota, USA.

ABSTRACT
Constipation affects up to a quarter of the population in developed countries and is associated with poor quality of life and significant economic burden. Many patients with chronic constipation are dissatisfied with current therapy due to lack of long-term efficacy or side effects. Previous nonselective 5-hydroxytryptamine receptor 4 (5-HT(4)) agonists have been associated with significant interactions with other receptors (5-HT(1B), 5-HT(1D), and 5-HT(2B) for tegaserod; hERG for cisapride), leading to adverse cardiovascular events resulting in withdrawal of these drugs from the market. Prucalopride is a novel gastrointestinal prokinetic agent. It acts as a high affinity, highly-selective 5-HT(4) agonist. Its efficacy in patients with chronic constipation has been demonstrated in several phase II and phase III clinical trials showing significant improvements in bowel transit, bowel function, gastrointestinal symptoms, and quality of life, with benefit maintained for up to 24 months in open label, multicenter, follow-up studies. Prucalopride's high selectivity for the 5-HT(4) receptor may explain its favorable safety and tolerability profiles, even in elderly subjects with stable cardiovascular disease. Prucalopride is a well tolerated and efficacious prokinetic medication that should enhance the treatment of chronic constipation unresponsive to first-line treatments.

No MeSH data available.


Related in: MedlinePlus