The effects of the specific 5HT₄ receptor agonist, prucalopride, on colonic motility in healthy volunteers

Abstract

Background: Prucalopride is a selective and specific 5‐hydroxytryptamine4 receptor agonist that is known to increase stool frequency and to accelerate colonic transit. Aim: To investigate the effect of prucalopride on high‐amplitude propagated contractions and segmental pressure waves in healthy volunteers. Methods: After 1 week of dosing (prucalopride or placebo in a double‐blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid‐state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High‐amplitude propagated contractions were analysed visually, comparing their total numbers and using 10‐min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks. Results: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high‐amplitude propagated contractions (P=0.055). The number of 10‐min time windows containing high‐amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026). Conclusions: The 5‐hydroxytryptamine4 receptor agonist prucalopride stimulates high‐amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.

Future Treatment of Constipation-associated Disorders: Role of Relamorelin and Other Ghrelin Receptor Agonists

“…The observed activity in the colon is comparable to the effects seen following a treatment with other colonic prokinetics such as prucalopride, or other serotonin receptor agonists or neostigmine; however, in contrast to the above mentioned drugs RM-131 exhibits a delayed effect (24-36 hour postadministration) on the colonic motility. [42][43][44] To further characterize the effects reported in the human colon the same group of authors evaluated the clinical efficacy of RM-131 in patients with confirmed CC. Similarly to their first clinical trial, the propulsive effects of RM-131 were confirmed, and the trial added that the duration of RM-131 is long-lasting with RM-131 activity being reported for a minimum of 1 hour.…”

Bloating and functional gastro-intestinal disorders: Where are we and where are we going?

“…For these reasons, its use in clinical practice is very limited. Prucalopride is a highly selective 5-HT4 receptor agonist with strong enterokinetic activity [124,125] and requires lower dose for this therapeutic effect [119] making this drug potentially suitable for bloating patients [126] . Itopride, a dopamine receptors antagonist and acetylcholinesterase inhibitor, has shown conflicting results in patients with functional dyspepsia [127,128] .…”

Relamorelin to Treat Constipation: “Pusher” or Pushover?

“…All in all, the available literature and those provided in the study suggest that since relamorelin might be considered as a relatively pure ''pusher,'' at least in the colon, this drug may be effective in the treatment of constipation, even though its propulsive effects seem to be relatively feeble when compared with those characteristic of other drugs [5][6][7][8]. Nevertheless, its ability to stimulate proximal gut motility [11] combined with its subcutaneous route of administration might benefit not only conventional constipated subjects, but also other subtypes of constipation such as in post-operative and neutrally compromised patients, and in patients refractory to all other medications [13].…”

“…Caution should, however, be the rule when interpretating such data, since some of these studies have been conducted only in healthy volunteers [6][7][8], and at least for one of them the findings have not been reproduced in either controls or patients [9]; therefore, further data, possibly obtained in patients with chronic constipation, would be indeed welcome.…”

“…Therefore, since drugs can increase the frequency and amplitude of colonic contractions, especially the manometric equivalents of mass movements, termed high-amplitude propagated contractions [4], such medications could prove useful tools in constipation treatment. To date, objective documentation in humans of such stimulation is available for only a few clinically available drugs, including bisacodyl [5], macrogol [6], chenodeoxycholic acid [7], and prucalopride [8].…”