title: Prucalopride, a systemic enterokinetic, for the treatment of constipation.
abstract: BACKGROUND
  Laxatives are frequently ineffective in treating constipation. An alternative therapeutic approach is to target serotonin-4 receptors, which are involved in initiating peristalsis.
  
  
  OBJECTIVE
  In a double-blind, placebo-controlled trial, to assess the efficacy and safety of a systemically active serotonin-4 agonist, prucalopride.
  
  
  METHODS
  Seventy-four women with constipation were stratified into slow or normal transit groups, and each group was randomized to receive either placebo or 1 mg prucalopride daily for 4 weeks. A bowel function diary was maintained. Whole-gut and orocaecal transit, visceral sensitivity, quality of life and psychological state were assessed before and after treatment.
  
  
  RESULTS
  Prucalopride, not placebo, increased spontaneous stool frequency (P=0.008) and reduced time to first stool (P < 0.001). Prucalopride reduced the number of retained markers in all patients compared to placebo (P=0.004). Prucalopride reduced the mean number of retained markers in slow transit (P=0.069), but did not alter the marker count in normal transit (P=0.86). Orocaecal transit was accelerated by prucalopride, not placebo (P=0.004). Prucalopride, notplacebo, increased rectal sensitivity to distension (urge volume, P=0.01) and electrical stimulation (P=0.001). Prucalopride significantly improved several domains of the Short Form Health Status Survey and the disease-specific quality of life. Adverse effects were similar for prucalopride and placebo.
  
  
  CONCLUSIONS
  Prucalopride improves symptoms, upper gut transit and gut sensitivity in constipated patients with both slow and normal transit. It improves transit in patients with slow transit. These changes are associated with improved well-being.
authors.affiliation: St. Mark's Hospital, Harrow, Middlesex, UK.
authors.forename: A V
authors.initials: AV
authors.lastname: Emmanuel
authors.forename: A J
authors.initials: AJ
authors.lastname: Roy
authors.forename: T J
authors.initials: TJ
authors.lastname: Nicholls
authors.forename: M A
authors.initials: MA
authors.lastname: Kamm
mesh_terms: D000328:Adult; D001572:Benzofurans / Q000009:adverse effects / Q000627:therapeutic use*; D002400:Cathartics / Q000627:therapeutic use*; D003248:Constipation / Q000188:drug therapy* / Q000503:physiopathology / Q000523:psychology; D003672:Defecation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects; D006801:Humans; D010349:Patient Compliance; D011788:Quality of Life; D012007:Rectum / Q000503:physiopathology; D017366:Serotonin Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001572:Benzofurans; D002400:Cathartics; D017366:Serotonin Receptor Agonists; C406662:prucalopride