Prokinetic effects of a new 5-HT4 agonist, YKP10811, on gastric motility in dogs

Jieyun Yin, Xiaohong Xu, Gengqing Song, Hyun Sil Han, Hong Wook Kim, Jiande Chen

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aim: Prokinetics have been considered the first-line medicine for treating delayed gastric emptying. The aim of this study was to explore the effects and mechanisms of a new 5-HT4 receptor agonist, YKP10811, on gastric motility in dogs. Methods: Four experiments were performed in dogs: (i) dose–response effects of YKP10811 on liquid gastric emptying; (ii) effects and mechanisms of YKP10811 on solid gastric emptying delayed by glucagon; (iii) effects of low-dose YKP10811 on antral contractions; and (iv) effects of low-dose YKP10811 on gastric accommodation. Results: No adverse events or cardiac dysrhythmia was noted. (i) High-dose YKP10811 (30 mg/kg) accelerated liquid gastric emptying from 15 to 90 min without inducing adverse events or cardiac dysrhythmia. YKP10811 at low doses (0.3, 1, and 3 mg/kg) accelerated gastric emptying in a dose-dependent manner. (ii) YKP10811 (0.1 mg/kg), but not tegaserod (0.3 mg/kg), significantly accelerated glucagon-induced delayed gastric emptying of solid, and the effect was completely blocked by GR113808. (iii) YKP10811 (0.3 mg/kg) enhanced antral contractions. (iv) YKP10811 did not alter gastric accommodation. Conclusions: YKP10811 seems to improve antral contractions and accelerate gastric emptying without altering gastric accommodation in dogs via the 5-HT4 mechanism and is substantially more potent than tegaserod. No adverse events were noted at a dose 300 times the lowest effective dose. YKP10811 may have a therapeutic potential for gastroparesis.

Original languageEnglish (US)
Pages (from-to)625-630
Number of pages6
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume32
Issue number3
DOIs
StatePublished - Mar 1 2017
Externally publishedYes

Keywords

  • 5-HT receptor agonists
  • gastric emptying
  • gastrointestinal motility
  • gastroparesis

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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