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Prokinetic effects of a new 5‐HT 4 agonist, YKP10811, on gastric motility in dogs
Author(s) -
Yin Jieyun,
Xu Xiaohong,
Song Gengqing,
Han Hyun Sil,
Kim Hong Wook,
Chen Jiande D Z
Publication year - 2017
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1111/jgh.13490
Subject(s) - gastric emptying , medicine , gastroparesis , antrum , cisapride , stomach , agonist , gastroenterology , adverse effect , prokinetic agent , receptor
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‐HT 4 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‐HT 4 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.