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YH12852, a potent and highly selective 5-HT4 receptor agonist, significantly improves both upper and lower gastrointestinal motility in a guinea pig model of postoperative ileus

Authors
 Z. Hussain  ;  Y. J. Lee  ;  H. Yang  ;  E. J. Jeong  ;  J. Y. Sim  ;  H. Park 
Citation
 NEUROGASTROENTEROLOGY AND MOTILITY, Vol.29(10) : 1-6, 2017-10 
Journal Title
NEUROGASTROENTEROLOGY AND MOTILITY
ISSN
 1350-1925 
Issue Date
2017-10
MeSH
Animals ; Disease Models, Animal ; Gastrointestinal Motility / drug effects* ; Guinea Pigs ; Ileus* ; Male ; Postoperative Complications ; Pyrimidines / pharmacology* ; Serotonin 5-HT4 Receptor Agonists / pharmacology*
Keywords
5-HT4 receptor agonist ; GR113808 ; YH12852 ; guinea pig ; postoperative ileus
Abstract
Background: Postoperative ileus (POI) is a transient gastrointestinal (GI) dysmotility that commonly develops after abdominal surgery. YH12852, a novel, potent and highly selective 5-hydroxytryptamine 4 (5-HT4 ) receptor agonist, has been shown to improve both upper and lower GI motility in various animal studies and may have applications for the treatment of POI. Here, we investigated the effects and mechanism of action of YH12852 in a guinea pig model of POI to explore its therapeutic potential.

Methods: The guinea pig model of POI was created by laparotomy, evisceration, and gentle manipulation of the cecum for 60 seconds, followed by closure with sutures under anesthesia. Group 1 received an oral administration of vehicle or YH12852 (1, 3, 10 or 30 mg/kg) only, while POI Group 2 was intraperitoneally pretreated with vehicle or 5-HT4 receptor antagonist GR113808 (10 mg/kg) prior to oral dosing of vehicle or YH12852 (3 or 10 mg/kg). Upper GI transit was evaluated by assessing the migration of a charcoal mixture in the small intestine, while lower GI transit was assessed via measurement of fecal pellet output (FPO).

Key results: YH12852 significantly accelerated upper and lower GI transit at the doses of 3, 10, and 30 mg/kg and reached its maximal effect at 10 mg/kg. These effects were significantly blocked by pretreatment of GR113808 10 mg/kg.

Conclusion and inferences: Oral administration of YH12852 significantly accelerates and restores delayed upper and lower GI transit in a guinea pig model of POI. This drug may serve as a useful candidate for the treatment of postoperative ileus.
Full Text
https://onlinelibrary.wiley.com/doi/10.1111/nmo.13094
DOI
10.1111/nmo.13094
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Park, Hyo Jin(박효진) ORCID logo https://orcid.org/0000-0003-4814-8330
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/195836
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