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

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Camilleri M, Vazquez-Roque MI, Burton D, Ford T, McKinzie S, Zinsmeister AR, Druzgala P

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

Neurogastroenterol Motil. 2007 Jan;19(1):30-8.

PubMed ID

17187586 [ View in PubMed

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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.

DrugBank Data that Cites this Article

Drugs

Naronapride

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Naronapride	5-hydroxytryptamine receptor 4	Protein	Humans	Unknown	Agonist	Details