Children's medicine of the North-West

Role of trimebutin as a pathogenetic therapy of functional diseases of the gastrointestinal tract in children and adolescents

GASTROENTEROLOGY AND DIETOLOGY

Keywords:
functional gastro-intestinal disorders motilin cholecystokinin trimebutine функциональные расстройства органов пищеварения мотилин холецистокинин тримебутин

Abstract

Introduction.Functional gastrointestinal disorders affect 12–30% of children and adolescents, significantly impairing quality of life. Dysregulation of gut motility with altered levels of motilin and cholecystokinin is a key pathogenetic mechanism. Trimebutine acts on opioid receptors in the gut, normalizing motility and visceral sensitivity, also act on motilin and cholecystokinin levels.The study aimedto evaluate the effect of trimebutine on abdominal pain, stool pattern, and serum motilin and cholecystokinin levels in children aged 3–17 years with functional gastrointestinal disorders.Materials and methods.A two-center prospective observational study included 64 patients (57 aged 6–17 years, 7 aged 3–5 years) with functional gastrointestinal disorders (functional dyspepsia, irritable bowel syndrome, functional biliary tract disorder, or overlap) were confirmed using Rome IV criteria. Patients received age-appropriate doses of trimebutine (Neobutin) for 28 days. Before and after treatment pain intensity was assessed with the Wong–Baker scale, stool consistency with the Bristol Stool Scale, serum motilin and cholecystokinin levels were measured.Results.After 4 weeks, overall improvement was reported in 70.3% of patients; clinically significant pain reduction (≥2 points) in 82.8%. Constipation prevalence decreased from 23.4% to 3.1%. Baseline motilin and cholecystokinin levels were elevated in 95.3% and 100% of patients, respectively. Trimebutine significantly reduced motilin by 207.5 pg/m L (p <0.001) in the overall cohort, and cholecystokinin by 28.0 pg/m L (p=0.045) in the 6–17 years group. No correlation was found between peptide reduction and analgesic effect (r=0.098). Treatment adherence exceeded 95%. Adverse events (mostly mild respiratory infections) occurred in 7.8%; no serious adverse events were recorded.Conclusion.Trimebutine (neobutin) is effective and safe for treating functional gastrointestinal disorders in children aged 3–17 years. It rapidly relieves pain, normalizes bowel habits, and reduces elevated motilin and cholecystokinin levels. Further placebo-controlled studies with larger samples of younger children are warranted.

Author Biographies

Natalia V. Baryshnikova, Saint Petersburg State Pediatric Medical University; Institute of Experimental Medicine

Cand. Sci. (Med.), Associate Professor, Associate Professor at the Department of Faculty Therapy named after Professor V.A. Waldman, Junior Researcher at the Laboratory of Medical and Social Problems of Pediatrics, Saint Petersburg State Pediatric Medical University; Researcher at the Laboratory of Molecular Microbiology, Institute of Experimental Medicine

Dinara R. Ismagilova, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

Chief of the Department of Diagnostics and Gastroenterology

Guzel M. Khadieva, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

gastroenterologist, Children’s Clinic “AZINO”, a structural subdivision of the of the Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

Olga N. Varlamova, Saint Petersburg State Pediatric Medical University

Researcher, Laboratory of Medical and Social Problems in Pediatrics, Research Center

Alexander E. Blinov, Saint Petersburg State Pediatric Medical University

Senior Researcher, Laboratory of Medical and Social Problems in Pediatrics, Research Center

Olga P. Gurina, Saint Petersburg State Pediatric Medical University

Cand. Sci. (Med.), Senior Researcher, Laboratory of Medical and Social Problems in Pediatrics, Research Center

Aelita A. Kamalova, Kazan State Medical University; Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

Dr. Sci. (Med.), Professor of the Department of Hospital Pediatrics, Kazan State Medical University; gastroenterologist and pediatrician of the Department of Diagnostics and Gastroenterology, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

Tatiana V. Mishkina, Saint Petersburg State Pediatric Medical University

Cand. Sci. (Med.), Associate Professor at the Department of Pediatrics named after Academician A.F. Tur

Alexey R. Bakhavalov, Saint Petersburg State Pediatric Medical University; Gatchina Clinical Interdistrict Hospital

Postgraduate Student, Department of Propaedeutics of Childhood Diseases named after Professor V.V. Yuriev, Saint Petersburg State Pediatric Medical University; Head of the Pediatric Department, Gatchina Clinical Interdistrict Hospital

Alina A. Petrik, Consulting and Diagnostic Center for Children

Head of the Abdominal Pathology Department

Margarita M. Gurova, Saint Petersburg State Pediatric Medical University; Consulting and Diagnostic Center for Children; Belgorod State National Research University

Dr. Sci. (Med.), Professor at the Department of Propaedeutics of Childhood Diseases named after Professor V.V. Yuriev, Leading Researcher at the Laboratory of Medical and Social Problems in Pediatrics, Research Center, Saint Petersburg State Pediatric Medical University; Professor at the Department of Pediatrics, Belgorod State National Research University; Deputy Chief Physician for Medical Affairs, Consultative and Diagnostic Center for Children

Valeria P. Novikova, Saint Petersburg State Pediatric Medical University

Dr. Sci. (Med.), Professor, Head of the Department of Propaedeutics of Childhood Diseases with a Course in General Child Care named after V.V. Yuryev

Chulpan I. Ashrafullina, Children’s Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan

chief of the 1 Paediatric Department

References

1. Drossman D.A., Hasler W.L. Rome IV-Functional GI Disorders: Disorders of Gut-Brain Interaction. Gastroenterology. 2016;150(6):1257–1261. https://doi.org/10.1053/j.gastro.2016.03.035.

2. Tran D.L., Sintusek P. Functional constipation in children: What physicians should know. World J Gastroenterol. 2023;29(8):1261–1288. https://doi.org/10.3748/wjg.v29.i8.1261.

3. Bueno L., Fioramonti J. Neurohormonal control of intestinal transit. Reprod Nutr Dev. 1994;34(6):513–525. https://doi.org/10.1051/rnd:19940601.

4. Deloose E., Janssen P., Depoortere I., Tack J. The migrating motor complex: control mechanisms and its role in health and disease. Nat Rev Gastroenterol Hepatol. 2012;9(5):271–285. https://doi.org/10.1038/nrgastro.2012.57.

5. Owyang C., Heldsinger A. Vagal control of satiety and hormonal regulation of appetite. J Neurogastroenterol Motil. 2011;17(4):338–348. https://doi.org/10.5056/jnm.2011.17.4.338.

6. Захарова И.Н., Сугян Н.Г., Бережная И.В. Функциональные гастроинтестинальные расстройства у детей раннего возраста: критерии диагностики и подходы к диетотерапии. Российский вестник перинатологии и педиатрии. 2018;63:(1):113–121. https://doi.org/10.21508/10274065-2018-63-1-113-121.

7. Ding F.C.L., Karkhaneh M., Zorzela L., Jou H., Vohra S. Probiotics for paediatric functional abdominal pain disorders: A rapid review. Paediatr Child Health. 2019;24(6):383–394. https://doi.org/10.1093/pch/pxz036.

8. Медведева Е.А., Хавкин А.И. Маски абдоминальной боли у детей дошкольного и раннего школьного возраста. РМЖ. Мать и дитя. 2023;6(2):175–183. https://doi.org/10.32364/2618-8430-2023-6-2-175-183.

9. Хавкин А.И., Новикова В.П., Гурова М.М. Особенности лекарственной терапии функциональных расстройств органов пищеварения у детей дошкольного и раннего школьного возраста. Медицинский совет. 2023;17(12):110–118. https://doi.org/10.21518/ms2023-215.

10. Roman F.J., Lanet S., Hamon J., Brunelle G., Maurin A., Champeroux P. et al. Pharmacological properties of trimebutine and N-monodesmethyltrimebutine. J Pharmacol Exp Ther. 1999;289(3):1391–1397.

11. Lee H.T., Kim B.J. Trimebutine as a modulator of gastrointestinal motility. Arch Pharm Res. 2011;34(6):861–864. https://doi.org/10.1007/s12272-011-0600-7.

12. Булгаков С.А. Пептиды опиоидной системы в регуляции пищевого поведения и аппетита. (Обзор литературы). Доказательная гастроэнтерология. 2024;13(1):79–85. https://doi.org/10.17116/dokgastro20241301179.

13. Karabulut G.S., Beşer O.F, Erginöz E., Kutlu T., Cokuğraş F.Ç., Erkan T. The incidence of irritable bowel syndrome in children using the Rome III Criteria and the effect of Trimebutine treatment. J Neurogastroenterol Motil. 2013;19(1):90–93. https://doi.org/10.5056/jnm.2013.19.1.90.

14. Успенский Ю.П., Барышникова Н.В., Гурова М.М., Новикова В.П. Функциональные расстройства ЖКТ у детей старшего возраста. В кн.: Руководство по педиатрии. Т. 6. Гастроэнтерология детского возраста. СПб.: Санкт-Петербургский государственный педиатрический медицинский университет; 2022. С. 174–260.

15. Бельмер С.В., Волынец Г.В., Горелов А.В. и др. Функциональные расстройства органов пищеварения у детей. Рекомендации Общества детских гастроэнтерологов, гепатологов и нутрициологов. Москва: Общество детских гастроэнтерологов, гепатологов и нутрициологов; 2021. 64 с.

16. Tomlinson D., von Baeyer C.L., Stinson J.N., Sung L. A systematic review of faces scales for the self-report of pain intensity in children. Pediatrics. 2010;126(5):e1168–1198. https://doi.org/10.1542/peds.2010-1609.

17. Lewis S.J., Heaton K.W. Stool form scale as a useful guide to intestinal transit time. Scand J Gastroenterol. 1997;32(9):920–924. https://doi.org/10.3109/ 00365529709011203.

18. Christensen M.F. Motilin in children with recurrent abdominal pain: a controlled study. Acta Paediatr. 1994;83(5): 542–544. https://doi.org/10.1111/j.1651-2227.1994.tb13076.x.

19. Sjölund K., Ekman R., Lindgren S., Rehfeld J.F. Disturbed motilin and cholecystokinin release in the irritable bowel syndrome. Scand J Gastroenterol. 1996;31(11):1110–1114. https://doi.org/10.3109/00365529609036895.

20. Zhang Y., Zhao J., Hu N., Wang J., Chen X., Wang K., Yin Y. Motilin and its receptor are expressed in the dorsal horn in a rat model of acute incisional pain: Intrathecal motilin injection alleviates pain behaviors. Front Neurosci. 2023;17:1104862. https://doi.org/10.3389/fnins.2023.1104862.

21. Alfvén G., Uvnäs-Moberg K. Elevated cholecystokinin concentrations in plasma in children with recurrent abdominal pain. Acta Paediatr. 1993;82(11):967–970. https://doi.org/10.1111/j.1651-2227.1993.tb12611.x.

22. Jonsson B.H., Uvnäs-Moberg K., Theorell T., Gotthard R. Gastrin, cholecystokinin, and somatostatin in a laboratory experiment of patients with functional dyspepsia. Psychosom Med. 1998;60(3):331–337. https://doi.org/10.1097/00006842-199805000-00020.

How to Cite
Role of trimebutin as a pathogenetic therapy of functional diseases of the gastrointestinal tract in children and adolescents: GASTROENTEROLOGY AND DIETOLOGY. (2026). Children’s Medicine of the North-West, 14(2), 157-170. https://doi.org/10.56871/
Issue
Vol. 14 No. 2 (2026)
Section
Original papers
Published
2026-07-30

How to Cite

Role of trimebutin as a pathogenetic therapy of functional diseases of the gastrointestinal tract in children and adolescents: GASTROENTEROLOGY AND DIETOLOGY. (2026). Children’s Medicine of the North-West, 14(2), 157-170. https://doi.org/10.56871/