J Neurogastroenterol Motil 2018; 24(4): 669-675  https://doi.org/10.5056/jnm18049
The Effect of Trimebutine on the Overlap Syndrome Model of Guinea Pigs
Zahid Hussain, Da Hyun Jung, Young Ju Lee, and Hyojin Park*
Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
Correspondence to: Hyojin Park, MD, PhD
Division of Gastroenterology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, 211, Eonju-ro, Gangnam-gu, Seoul 06273, Korea
Tel: +82-2-2019-3318, Fax: +82-2-3463-3882, E-mail: hjpark21@yuhs.ac
Received: March 3, 2018; Revised: May 11, 2018; Accepted: June 12, 2018; Published online: October 1, 2018.
© The Korean Society of Neurogastroenterology and Motility. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background/Aims
Functional dyspepsia (FD) and irritable bowel syndrome (IBS) are common gastrointestinal (GI) disorders and these patients frequently overlap. Trimebutine has been known to be effective in controlling FD co-existing diarrhea-dominant IBS, however its effect on overlap syndrome (OS) patients has not been reported. Therefore, we investigated the effect of trimebutine on the model of OS in guinea pigs.
Methods
Male guinea pigs were used to evaluate the effects of trimebutine in corticotropin-releasing factor (CRF) induced OS model. Different doses (3, 10, and 30 mg/kg) of trimebutine were administered orally and incubated for 1 hour. The next treatment of 10 μg/kg of CRF was intraperitoneally injected and stabilized for 30 minutes. Subsequently, intragastric 3 mL charcoal mix was administered, incubated for 10 minutes and the upper GI transit analyzed. Colonic transits were assessed after the same order and concentrations of trimebutine and CRF treatment by fecal pellet output assay.
Results
Different concentrations (1, 3, and 10 μg/kg) of rat/human CRF peptides was tested to establish the OS model in guinea pigs. CRF 10 μg/kg was the most effective dose in the experimental OS model of guinea pigs. Trimebutine (3, 10, and 30 mg/kg) treatment significantly reversed the upper and lower GI transit of CRF induced OS model. Trimebutine significantly increased upper GI transit while it reduced fecal pellet output in the CRF induced OS model.
Conclusions
Trimebutine has been demonstrated to be effective on both upper and lower GI motor function in peripheral CRF induced OS model. Therefore, trimebutine might be an effective drug for the treatment of OS between FD and IBS patients.
Keywords: Corticotropin-releasing factor; Guinea pigs; Overlap syndrome; Trimebutine


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