Pharmacodynamic effects of a novel prokinetic 5-HT 4 receptor agonist, ATI-7505, in humans

M. Camilleri, M. I. Vazquez-Roque, D. Burton, T. Ford, S. McKinzie, A. R. Zinsmeister, P. Druzgala

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

ATI-7505, an investigational 5-HT 4 receptor agonist, was designed to have similar activity as cisapride without the cardiac adverse effects, i.e. without QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and colonic transit in healthy humans. A randomized, parallel-group, double-blind, placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3, 10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers (12 per group). Primary endpoints were gastric-emptying (GE) T 1/2, colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T 1/2. Daily stool diaries were kept. Analysis of covariance assessed overall treatment group differences, followed by post hoc unadjusted pairwise comparisons. There were borderline overall treatment effects (decrease) on GE T 1/2 (P = 0.154); the 20 mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo (P = 0.065). ATI-7505 accelerated AC emptying T 1/2 (overall P = 0.075) with 10 mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale, overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were identified. ATI-7505 accelerates overall colonic transit and tends to accelerate GE and AC emptying and loosen stool consistency.

Original languageEnglish (US)
Pages (from-to)30-38
Number of pages9
JournalNeurogastroenterology and Motility
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2007

Keywords

  • 5-HT receptor
  • ATI-7505
  • Agonist
  • Serotonin

ASJC Scopus subject areas

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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