Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation

Neurogastroenterol Motil. 2010 Jan;22(1):42-9, e7-8. doi: 10.1111/j.1365-2982.2009.01378.x. Epub 2009 Aug 18.


Velusetrag (TD-5108) is a potent, selective high intrinsic activity serotonin 5-HT(4) receptor agonist. We assessed effects of Velusetrag on gastrointestinal transit and compared its pharmacokinetics in healthy volunteers (HV) and chronic constipation (CC) patients. Sixty HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg Velusetrag (single and 6-day dosing). Primary endpoints were colonic transit (geometric centre at 24 h, GC24) and ascending colon emptying (ACE) T(1/2) after first dose. Secondary endpoints included gastric emptying (GE) T(1/2) and colonic filling at 6 h (CF6). Single dose Velusetrag significantly accelerated GC24, ACE T(1/2), and CF6; 30 and 50 mg Velusetrag accelerated all three endpoints. With multiple doses, Velusetrag 30 mg accelerated GC24, and overall accelerated GE T(1/2) at 15-50 mg. Pharmacokinetics studies showed dose proportionality in health, and no significant differences between health and chronic constipation with a 15 mg oral dose of Velusetrag. Stimulation of bowel function after15 mg Velusetrag was similar in CC and controls. There were no serious adverse events; notable adverse events were the predictable gastrointestinal effects such as diarrhoea or altered bowel movements. Velusetrag significantly accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing. Further studies of its potential as a gastrointestinal and colonic prokinetic are warranted.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Azabicyclo Compounds* / pharmacokinetics
  • Azabicyclo Compounds* / pharmacology
  • Azabicyclo Compounds* / therapeutic use
  • Constipation / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Gastrointestinal Agents* / pharmacokinetics
  • Gastrointestinal Agents* / pharmacology
  • Gastrointestinal Agents* / therapeutic use
  • Gastrointestinal Motility / drug effects*
  • Gastrointestinal Motility / physiology
  • Gastrointestinal Transit / drug effects*
  • Gastrointestinal Transit / physiology
  • Humans
  • Intestines / drug effects
  • Intestines / physiology
  • Male
  • Middle Aged
  • Placebos / therapeutic use
  • Pregnancy
  • Young Adult


  • Azabicyclo Compounds
  • Gastrointestinal Agents
  • Placebos
  • TD-5108