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Prokinetics in the Management of Functional Gastrointestinal Disorders

  • Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract (S Rao, Section Editor)
  • Published:
Current Gastroenterology Reports Aims and scope Submit manuscript

Abstract

Purpose of review

The goal of this review is to review the current status of prokinetics and to place it in historical context. Impaired motility and thus propulsion have long been thought to play important roles in the pathogenesis of a number of gastrointestinal disorders including gastroesophageal reflux disease (GERD), gastroparesis, chronic idiopathic pseudo-obstruction, and constipation. Historically, disordered motility was also thought to contribute to a number of functional gastrointestinal disorders such as functional dyspepsia (FD) and irritable bowel syndrome (IBS).

Recent findings

As we learn more of the pathophysiology of FD, IBS, GERD, constipation, and gastroparesis, the limitations of a therapeutic strategy based on the stimulation of motility (i.e., the use of a prokinetic) have become apparent and the disappointments of the past explained. The development of prokinetic drugs has also been hampered by the non-selective nature of many of the agents studied to date which resulted in some unexpected side effects.

Summary

There is still an unmet need for an effective and safe prokinetic, but drug development in this area must be mindful of the challenges of the area and the need for selectivity for a given target receptor.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Camilleri M. Pharmacological agents currently in clinical trials for disorders in neurogastroenterology. J Clin Invest. 2013;123:4111–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Quigley EMM. The clinical pharmacology of motility disorders: the perils (and pearls) of prokinesia. Gastroenterology. 1994;106:1112–4.

    Article  CAS  PubMed  Google Scholar 

  3. • Stanghellini V, Tack J. Gastroparesis: separate entity or just a part of dyspepsia? Gut. 2014;63:1972–8. Critically addresses the challenges that the concept of gastroparesis presents and what that means for its therapy.

    Article  PubMed  Google Scholar 

  4. Dinning PG, Zarate N, Hunt LM, Fuentealba SE, Mohammed SD, Szczesniak MM, et al. Pancolonic spatiotemporal mapping reveals regional deficiencies in, and disorganization of colonic propagating pressure waves in severe constipation. Neurogastroenterol Motil. 2010;22:e340–9.

    Article  CAS  PubMed  Google Scholar 

  5. • Dinning PG, Wiklendt L, Maslen L, Patton V, Lewis H, Arkwright JW, et al. Colonic motor abnormalities in slow transit constipation defined by high resolution, fibre-optic manometry. Neurogastroenterol Motil. 2015;27:379–88. Reveals that hypomotility is not the main motor abnormality in the colon in constipation.

    Article  CAS  PubMed  Google Scholar 

  6. Videlock EJ, Lembo A, Cremonini F. Diagnostic testing for dyssynergic defecation in chronic constipation: meta-analysis. Neurogastroenterol Motil. 2013;25:509–20.

    Article  CAS  PubMed  Google Scholar 

  7. Lee TH, Lee JS, Hong SJ, Jeon SR, Kwon SH, Kim WJ, et al. Rectal hyposensitivity and functional anorectal outlet obstruction are common entities in patients with functional constipation but are not significantly associated. Korean J Intern Med. 2013;28:54–61.

    Article  PubMed  Google Scholar 

  8. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, et al. Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur J Pharmacol. 2010;649:328–35.

    Article  CAS  PubMed  Google Scholar 

  9. •• Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel disorders. Gastroenterology. 2016. The latest iteration of the Rome process on irritable bowel syndrome and constipation.

  10. Quigley EMM. The “con” case. The Rome process and functional gastrointestinal disorders: the barbarians are at the gate! Neurogastroenterol Motil. 2007;19:793–7.

    Article  CAS  PubMed  Google Scholar 

  11. Quigley EMM. Cisapride. What can we learn from the rise and fall of a prokinetic? J Dig Dis. 2011;12:147–56.

    Article  CAS  PubMed  Google Scholar 

  12. Tack J, Camilleri M, Chang L, Chey WD, Galligan JJ, Lacy BE, et al. Systematic review: cardiovascular safety profile of 5HT4 agonists developed for gastrointestinal disorders. Aliment Pharmacol Ther. 2012;35:745–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Quigley EMM. Prucalopride: safety, efficacy and potential applications. Ther Adv Gastroenterol. 2012;5:23–30.

    Article  CAS  Google Scholar 

  14. Tack J, Broeckaert D, Coulie B, Janssens J. The influence of cisapride on gastric tone and the perception of gastric distension. Aliment Pharmacol Ther. 1998;12:761–6.

    Article  CAS  PubMed  Google Scholar 

  15. Tack J, Caenepeel P, Piessevaux H, Cuomo R, Janssens J. Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia. Gut. 2003;52:1271–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Quigley EMM. Why do we have so few effective drugs for irritable bowel syndrome? A European perspective. Nat Clin Pract Gastroenterol Hepatol. 2005;2:436–7.

    Article  PubMed  Google Scholar 

  17. Malagelada J-R, Rees WDW, Mazzotta LJ. Gastric motor abnormalities in diabetic and post-vagotomy gastroparesis: effect of metoclopramide and bethanechol. Gastroenterology. 1980;78:286.

    CAS  PubMed  Google Scholar 

  18. Ponec RJ, Saunders MD, Kimmey MB. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med. 1999;341:137–41.

    Article  CAS  PubMed  Google Scholar 

  19. van der Spoel JI, Oudemans-van Straaten HM, Stoutenbeek CP, Bosman RJ, Zandstra DF. Neostigmine resolves critical illness-related colonic ileus in intensive care patients with multiple organ failure—a prospective, double-blind, placebo-controlled trial. Intensive Care Med. 2001;27:822–7.

    Article  PubMed  Google Scholar 

  20. Mehta R, John A, Nair P, Raj VV, Mustafa CP, Suvarna D, et al. Factors predicting successful outcome following neostigmine therapy in acute colonic pseudo-obstruction: a prospective study. J Gastroenterol Hepatol. 2006;21:459–61.

    Article  CAS  PubMed  Google Scholar 

  21. Cherta I, Forné M, Quintana S, Garriga MR, González de Molina FJ. Prolonged treatment with neostigmine for resolution of acute colonic pseudo-obstruction. Aliment Pharmacol Ther. 2006;23:1678–9.

    Article  CAS  PubMed  Google Scholar 

  22. Tsirline VB, Zemlyak AY, Avery MJ, Colavita PD, Christmas AB, Heniford BT, et al. Colonoscopy is superior to neostigmine in the treatment of Ogilvie’s syndrome. Am J Surg. 2012;204:849–55.

    Article  CAS  PubMed  Google Scholar 

  23. Caliskan E, Turkoz A, Sener M, Bozdogan N, Gulcan O, Turkoz R. A prospective randomized double-blind study to determine the effect of thoracic epidural neostigmine on postoperative ileus after abdominal aortic surgery. Anesth Analg. 2008;106:959–64.

    Article  CAS  PubMed  Google Scholar 

  24. Rubiales AS, Hernansanz S, Gutiérrez C, Del Valle ML, Flores LA. Neostigmine for refractory constipation in advanced cancer patients. J Pain Symptom Manag. 2006;32:204–5.

    Article  Google Scholar 

  25. Ong SP, Choong CF. Neostigmine in the treatment of severe constipation. Intern Med J. 2007;37:836–7.

    Article  CAS  PubMed  Google Scholar 

  26. Rosman AS, Chaparala G, Monga A, Spungen AM, Bauman WA, Korsten MA. Intramuscular neostigmine and glycopyrrolate safely accelerated bowel evacuation in patients with spinal cord injury and defecatory disorders. Dig Dis Sci. 2008;53:2710–3.

    Article  CAS  PubMed  Google Scholar 

  27. Law NM, Bharucha AE, Undale AS, Zinsmeister AR. Cholinergic stimulation enhances colonic motor activity, transit, and sensation in humans. Am J Physiol Gastrointest Liver Physiol. 2001;281:G1228–37.

    CAS  PubMed  Google Scholar 

  28. • Mouchli MA, Camilleri M, Lee T, Parthasarathy G, Vijayvargiya P, Halland M, et al. Evaluating the safety and the effects on colonic compliance of neostigmine during motility testing in patients with chronic constipation. Neurogastroenterol Motil. 2016;28:871–8. New life for an old drug. As new molecules fall by the wayside this study shows how an old molecule can be harnessed to benefit in constipation.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Bharucha AE, Low PA, Camilleri M, Burton D, Gehrking TL, Zinsmeister AR. Pilot study of pyridostigmine in constipated patients with autonomic neuropathy. Clin Auton Res. 2008;18:194–202.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Bharucha AE, Low P, Camilleri M, Veil E, Burton D, Kudva Y, et al. A randomised controlled study of the effect of cholinesterase inhibition on colon function in patients with diabetes mellitus and constipation. Gut. 2013;62:708–15.

    Article  CAS  PubMed  Google Scholar 

  31. • Parthasarathy G, Ravi K, Camilleri M, Andrews C, Szarka LA, Low PA, et al. Effect of neostigmine on gastroduodenal motility in patients with suspected gastrointestinal motility disorders. Neurogastroenterol Motil. 2015;27:1736–46. Another example of innovation using an old molecule.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. •• Acosta A, Camilleri M. Prokinetics in gastroparesis. Gastroenterol Clin N Am. 2015;44:97–111. A definitive review.

    Article  Google Scholar 

  33. Ogishima M, Kaibara M, Ueki S, Kurimoto T, Taniyama K. Z-338 facilitates acetylcholine release from enteric neurons due to blockade of muscarinic autoreceptors in guinea pig stomach. J Pharmacol Exp Ther. 2000;294:33–7.

    CAS  PubMed  Google Scholar 

  34. Matsunaga Y, Tanaka T, Yoshinaga K, Ueki S, Hori Y, Eta R, et al. Acotiamide hydrochloride (Z-338), a new selective acetylcholinesterase inhibitor, enhances gastric motility without prolonging QT interval in dogs: comparison with cisapride, itopride, and mosapride. J Pharmacol Exp Ther. 2011;336:791–800.

    Article  CAS  PubMed  Google Scholar 

  35. Tack J, Masclee A, Heading R, Berstad A, Piessevaux H, Popiela T, et al. A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia. Neurogastroenterol Motil. 2009;21:272–80.

    Article  CAS  PubMed  Google Scholar 

  36. Zai H, Matsueda K, Kusano M, Urita Y, Saito Y, Kato H. Effect of acotiamide on gastric emptying in healthy adult humans. Eur J Clin Investig. 2014;44:1215–21.

    Article  CAS  Google Scholar 

  37. Nakamura K, Tomita T, Oshima T, Asano H, Yamasaki T, Okugawa T, et al. A double-blind placebo controlled study of acotiamide hydrochloride for efficacy on gastrointestinal motility of patients with functional dyspepsia. J Gastroenterol. 2017;52:602–10.

    Article  CAS  PubMed  Google Scholar 

  38. Matsueda K, Hongo M, Tack J, Aoki H, Saito Y, Kato H. Clinical trial: dose-dependent therapeutic efficacy of acotiamide hydrochloride (Z-338) in patients with functional dyspepsia—100 mg t.i.d. is an optimal dosage. Neurogastroenterol Motil. 2010;22:618–e173.

    Article  CAS  PubMed  Google Scholar 

  39. Matsueda K, Hongo M, Tack J, Saito Y, Kato H. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia. Gut. 2012;61:821–8.

    Article  CAS  PubMed  Google Scholar 

  40. Xiao G, Xie X, Fan J, Deng J, Tan S, Zhu Y, et al. Efficacy and safety of acotiamide for the treatment of functional dyspepsia: systematic review and meta-analysis. ScientificWorldJournal. 2014;2014:541950.

    PubMed  PubMed Central  Google Scholar 

  41. Shinozaki S, Osawa H, Sakamoto H, Hayashi Y, Kawarai Lefor A, Yamamoto H. The effect of acotiamide on epigastric pain syndrome and postprandial distress syndrome in patients with functional dyspepsia. J Med Investig. 2016;63:230–5.

    Article  Google Scholar 

  42. Yamashita H, Kanamori A, Fukuchi T, Tsujimae M, Koizumi A, Iwatsubo T, et al. Novel prokinetic acotiamide reduces transient lower esophageal sphincter relaxation in healthy subjects. Digestion. 2015;92:90–8.

    Article  CAS  PubMed  Google Scholar 

  43. Ishimura N, Mori M, Mikami H, Shimura S, Uno G, Aimi M, et al. Effects of acotiamide on esophageal motor function and gastroesophageal reflux in healthy volunteers. BMC Gastroenterol. 2015;15:117.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Barone JA. Domperidone: a peripherally acting dopamine 2-receptor antagonist. Ann Pharmacol. 1999;33:429.

    Article  CAS  Google Scholar 

  45. Tonini M, Cipollina L, Poluzzi E, et al. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics. Aliment Pharmaol Ther. 2004;19:379.

    Article  CAS  Google Scholar 

  46. Lata PF, Pigarelli DL. Chronic metoclopramide therapy for diabetic gastroparesis. Curr Pharmacother. 2003;37:122.

    Article  CAS  Google Scholar 

  47. Ganzini L, Casey DE, Haffman WF, et al. The prevalence of metoclopramide-induced tardive dyskinesia and acute extrapyramidal movements. Arch Intern Med. 1993;153:1469.

    Article  CAS  PubMed  Google Scholar 

  48. Kenney C, Hunter C, Davidson A, Jankovic J. Metoclopramide, an increasingly recognized cause of tardive dyskinesia. J Clin Pharmacol. 2008;48:379–84.

    Article  CAS  PubMed  Google Scholar 

  49. Ehrenpreis ED, Deepak P, Sifuentes H, Devi R, Du H, Leikin JB. The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol. 2013;108:866–72.

    Article  CAS  PubMed  Google Scholar 

  50. https://www.fda.gov/downloads/drugs/drugsafety/ucm176362.pdf. Accessed 2 July 2017.

  51. Kaplan S, Staffa JA, Dal Pan GJ. Duration of therapy with metoclopramide: a prescription claims data study. Pharmacoepidemiol Drug Saf. 2007;16:878–81.

    Article  CAS  PubMed  Google Scholar 

  52. Pasricha PJ, Pehlivanov N, Sugumar A, Jankovic J. Drug insight: from disturbed motility to disordered movement--a review of the clinical benefits and medicolegal risks of metoclopramide. Nat Clin Pract Gastroenterol Hepatol. 2006;3:138–48.

    Article  CAS  PubMed  Google Scholar 

  53. Lee A, Kuo B. Metoclopramide in the treatment of diabetic gastroparesis. Expert Rev Endocrinol Metab. 2010;5:653–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dhakal OP, Dhakal M, Bhandari D. Domperidone-induced dystonia: a rare and troublesome complication. BMJ Case Rep. 2014;27:2014.

    Google Scholar 

  55. Horowitz M, Harding PE, Chatterton BE, et al. Acute and chronic effects of domperidone on gastric emptying in diabetic autonomic neuropathy. Dig Dis Sci. 1985;30:1.

    Article  CAS  PubMed  Google Scholar 

  56. Kranzese A, Borrelli O, Corrado G, et al. Domperidone is more effective than cisapride in children with diabetic gastroparesis. Aliment Pharmacol Ther. 2002;16:951.

    Article  Google Scholar 

  57. Parkman HP, Jacobs MR, Mishra A, Hurdle JA, Sachdeva P, Gaughan JP, et al. Domperidone treatment for gastroparesis: demographic and pharmacogenetic characterization of clinical efficacy and side-effects. Dig Dis Sci. 2011;56:115–24.

    Article  CAS  PubMed  Google Scholar 

  58. •• Schey R, Saadi M, Midani D, Roberts AC, Parupalli R, Parkman HP. Domperidone to treat symptoms of gastroparesis: benefits and side effects from a large single-center cohort. Dig Dis Sci. 2016;61:3545–51. Though neither prospective or an RCT provides a “real world” view of the use of domperidone in gastroparesis in the US.

    Article  CAS  PubMed  Google Scholar 

  59. Lidor AO, Ensor CR, Sheer AJ, Orens JB, Clarke JO, McDyer JF. Domperidone for delayed gastric emptying in lung transplant recipients with and without gastroesophageal reflux. Prog Transplant. 2014;24:27–32.

    Article  PubMed  Google Scholar 

  60. Westerhof J, Weersma RK, Hoedemaker RA, Koornstra JJ. Completion rate of small bowel capsule endoscopy is higher after erythromycin compared to domperidone. BMC Gastroenterol. 2014;14:162.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Hu B, Ye H, Sun C, Zhang Y, Lao Z, Wu F, et al. Metoclopramide or domperidone improves post-pyloric placement of spiral nasojejunal tubes in critically ill patients: a prospective, multicenter, open-label, randomized, controlled clinical trial. Crit Care. 2015;19:61.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Hondeghem LM. Domperidone: limited benefits with significant risk for sudden cardiac death. J Cardiovasc Pharmacol. 2013;61:218–25.

    Article  CAS  PubMed  Google Scholar 

  63. Makari J, Cameron K, Battistella M. Domperidone-associated sudden cardiac death in the general population and implications for use in patietns undergoing hemodialysis: a literature review. Can J Hosp Pharm. 2014;67:441–6.

    PubMed  PubMed Central  Google Scholar 

  64. Kanji S, Stevenson A, Hutton B. Sudden cardiac death and ventricular arrhythmias associated with domperidone: evidence supporting health Canada’s warning. Can J Hosp Pharm. 2014;67:311–2.

    PubMed  PubMed Central  Google Scholar 

  65. Arana A, Johannes CB, McQuay LJ, Varas-Lorenzo C, Fife D, Rothman KJ. Risk of out-of-hospital sudden cardiac death in users of domperidone, proton pump inhibitors, or metoclopramide: a population-based nested case-control study. Drug Saf. 2015;38:1187–99.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. • Leelakanok N, Holcombe A, Schweizer ML. Domperidone and risk of ventricular arrhythmia and cardiac death: a systematic review and meta-analysis. Clin Drug Investig. 2016;36:97–107. Real concern for the safety of this drug.

    Article  CAS  PubMed  Google Scholar 

  67. Renoux C, Dell’Aniello S, Khairy P, Marras C, Bugden S, Turin TC, et al. Ventricular tachyarrhythmia and sudden cardiac death with domperidone use in Parkinson’s disease. Br J Clin Pharmacol. 2016;82:461–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Forbes N, Cooray M, Al-Dabbagh R, Yuan Y, Tse F, Liu LW, et al. Domperidone prescribing practices exposed patients to cardiac risk despite a ‘black box’ warning: a Canadian tertiary care centre study. Can J Gastroenterol Hepatol. 2016;2016:2937678.

  69. Rojas-Fernandez C, Stephenson AL, Fischer HD, Wang X, Mestre T, Hutson JR, et al. Current use of domperidone and co-prescribing of medications that increase its arrhythmogenic potential among older adults: a population-based cohort study in Ontario, Canada. Drugs Aging. 2014;31:805–13.

    Article  CAS  PubMed  Google Scholar 

  70. Frommeyer G, Fischer C, Ellermann C, Lange PS, Dechering DG, Kochhäuser S, Fehr M, Eckardt L. Severe proarrhythmic potential of the antiemetic agents ondansetron and domperidone. Cardiovasc Toxicol. 2017.

  71. Morris AD, Chen J, Lau E, Poh J. Domperidone-associated QT interval prolongation in non-oncologic pediatric patients: a review of the literature. Can J Hosp Pharm. 2016;69:224–30.

    PubMed  PubMed Central  Google Scholar 

  72. Biewenga J, Keung C, Solanki B, Natarajan J, Leitz G, Deleu S, et al. Absence of QTc prolongation with domperidone: a randomized, double-blind, placebo- and positive-controlled thorough QT/QTc study in healthy volunteers. Clin Pharmacol Drug Dev. 2015;4:41–8.

    Article  CAS  PubMed  Google Scholar 

  73. Grzeskowiak LE, Amir LH. Use of domperidone to increase breast milk supply: further consideration of the benefit-risk ratio is required. J Hum Lact. 2015;31:315–6.

    Article  PubMed  Google Scholar 

  74. Melga P, Mansi C, Ciuchi E, et al. Chronic administration of levosulpiride and glycemic control in IDDM patients with gastroparesis. Diabetes Care. 1997;20:55.

    Article  CAS  PubMed  Google Scholar 

  75. Corazza GR, Biagi F, Albano O, et al. Levosulpiride in functional dyspepsia: a multicentric, double-blind, controlled trial. Ital J Gastroenterol. 1996;28:317.

    CAS  PubMed  Google Scholar 

  76. Mansi C, Borro P, Giacomini M, et al. Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis. Aliment Pharmacol Ther. 2000;14:561.

    Article  CAS  PubMed  Google Scholar 

  77. Mearin F, Rodrigo L, Pérez-Mota A, Balboa A, Jiménez I, Sebastián JJ, Patón C. Levosulpiride and cisapride in the treatment of dysmotility-like functional dyspepsia: a randomized, double-masked trial. Clin Gastroenterol Hepatol.

  78. Lozano R, Concha MP, Montealegre A, de Leon L, Villalba JO, Esteban HL, et al. Effectiveness and safety of levosulpiride in the treatment of dysmotility-like functional dyspepsia. Ther Clin Risk Manag. 2007;3:149–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Mendhekar DN, Gupta N. Combination therapy of levosulpiride and lamotrigine associated with tardive dyskinesia. Aust N Z J Psychiatry. 2009;43:178–9.

    PubMed  Google Scholar 

  80. Shin HW, Kim MJ, Kim JS, Lee MC, Chung SJ. Levosulpiride-induced movement disorders. Mov Disord. 2009;24:2249–53.

    Article  PubMed  Google Scholar 

  81. Kim HJ, Cho JY, Cho YJ, Hong KS. Levosulpiride-induced resting orolingual tremor. Mov Disord. 2009;24:1700–1.

    Article  PubMed  Google Scholar 

  82. Lee HC, Hwang SH, Kang SY. Levosulpiride-associated hemichorea. Yonsei Med J. 2016;57:803–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Mathew T, Nadimpally US, Prabhu AD, Nadig R. Drug-induced parkinsonism on the rise: beware of levosulpiride and its combinations with proton pump inhibitors. Neurol India. 2017;65:173–4.

    Article  PubMed  Google Scholar 

  84. Agosti S, Casalino L, Bertero G, Burrone A, Brunelli C, Morelloni S. Citalopram and levosulpiride: a dangerous drug combination for QT prolongation. Am J Emerg Med. 2013;31:1624.

    Article  PubMed  Google Scholar 

  85. Tsubouchi T, Saito T, Mizutani F, Yamauchi T, Iwanaga Y. Stimulatory action of itopride hydrochloride on colonic motor activity in vitro and in vivo. J Pharmacol Exp Ther. 2003;306:787–93.

    Article  CAS  PubMed  Google Scholar 

  86. Huang X, Lv B, Zhang S, Fan YH, Meng LN. Itopride therapy for functional dyspepsia: a meta-analysis. World J Gastroenterol. 2012;18:7371–7.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Talley NJ, Tack J, Ptak T, Gupta R, Giguère M. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut. 2008;57:740–6.

    Article  CAS  PubMed  Google Scholar 

  88. Holtmann G, Talley NJ, Liebregts T, Adam B, Parow C. A placebo-controlled trial of itopride in functional dyspepsia. N Engl J Med. 2006;354:832–40.

    Article  CAS  PubMed  Google Scholar 

  89. Camilleri M, Malagelada J-R, Abell TL, et al. Effect of six weeks of treatment with cisapride in gastroparesis and intestinal pseudo-obstruction. Gastroenterology. 1989;96:705.

    Google Scholar 

  90. Abell TL, Camilleri M, DiMagno EP, et al. Long-term efficacy of oral cisapride in symptomatic upper gut dysmotility. Dig Dis Sci. 1991;36:621.

    Article  Google Scholar 

  91. Vitola J, Vukanovic J, Roden DM. Cisapride-induced torsades de pointes. J Cardiovasc Electrophysiol. 1998;9:1109.

    Article  CAS  PubMed  Google Scholar 

  92. Wang SH, Lin CY, Huang TY, et al. QT interval effects of cisapride in the clinical setting. Int J Cardiol. 2001;80:179.

    Article  CAS  PubMed  Google Scholar 

  93. Prather CM, Camilleri M, Zimsmeister AR, et al. Tegaserod accelerates orocecal transit in patients with constipation-predominant irritable bowel syndrome. Gastroenterology. 2000;118:463.

    Article  CAS  PubMed  Google Scholar 

  94. Kahrilas PJ, Quigley EMM, Castell DO, et al. The effects of tegaserod (HFT 919) on oesophageal acid exposure in gastro-oesophageal reflux disease. Aliment Pharmacol Ther. 2000;14:1503.

    Article  CAS  PubMed  Google Scholar 

  95. Tack J, Vos R, Janssens J, et al. Influence of tegaserod on proximal gastric tone and on the perception of gastric distension. Aliment Pharmacol Ther. 2003;18:1031.

    Article  CAS  PubMed  Google Scholar 

  96. Busti AJ, Murillo JR Jr, Cryer B. Tegaserod-induced myocardial infarction: case report and hypothesis. Pharmacotherapy. 2004;24:526–31.

    Article  PubMed  Google Scholar 

  97. Sanger GJ, Quigley EMM. Constipation, IBS and the 5-HT4 receptor: what role for prucalopride? Clin Med Insights: Gastroenterology. 2010;3:21–33.

    CAS  Google Scholar 

  98. Potet F, Bouyssou T, Escande D, Baro I. Gastrointestinal prokinetic drugs have different affinity for the human cardiac human ether-a-gogo K(+) channel. J Pharmacol Exp Ther. 2001;299:1007–12.

    CAS  PubMed  Google Scholar 

  99. Mendzelevski B, Ausma J, Chanter DO, et al. Assessment of the cardiac safety of prucalopride in healthy volunteers: a randomized, double-blind, placebo- and positive-controlled thorough QT study. Br J Clin Pharmacol. 2012;73:203–9.

  100. Bouras EP, Camilleri M, Burton DD, McKinzie S. Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut. 1999;44:682–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology. 2001;120:354–60.

    Article  CAS  PubMed  Google Scholar 

  102. Kessing BF, Smout AJ, Bennink RJ, Kraaijpoel N, Oors JM, Bredenoord AJ. Prucalopride decreases esophageal acid exposure and accelerates gastric emptying in healthy subjects. Neurogastroenterol Motil. 2014;26:1079–86.

    Article  CAS  PubMed  Google Scholar 

  103. • Bianco F, Bonora E, Natarajan D, Vargiolu M, Thapar N, Torresan F, et al. Prucalopride exerts neuroprotection in human enteric neurons. Am J Physiol Gastrointest Liver Physiol. 2016;310:G768–75. An interesting observation of potential relevance to neuropathic motility disorders.

    Article  PubMed  PubMed Central  Google Scholar 

  104. Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. New Engl J Med. 2008;358:2344–54.

    Article  CAS  PubMed  Google Scholar 

  105. Tack J, van Outryve M, Beyens G, et al. Prucalopride (Resolor) in the treatment of severe chronic constipation in patients dissatisfied with laxatives. Gut. 2009;58:357–65.

    Article  CAS  PubMed  Google Scholar 

  106. Quigley EM, Vandeplassche L, Kerstens R, Ausma J. Clinical trial: the efficacy, impact on quality of life, and safety and tolerability of prucalopride in severe chronic constipation—a 12-week, randomized, double-blind, placebo-controlled study. Aliment Pharmacol Ther. 2009;29:315–28.

    Article  CAS  PubMed  Google Scholar 

  107. Ke M, Zou D, Yuan Y, Li Y, Lin L, Hao J, et al. Prucalopride in the treatment of chronic constipation in patients from the Asia-Pacific region: a randomized, double-blind, placebo-controlled study. Neurogastroenterol Motil. 2012;24:999–e541.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mugie SM, Korczowski B, Bodi P, Green A, Kerstens R, Ausma J, et al. Prucalopride is no more effective than placebo for children with functional constipation. Gastroenterology. 2014;147:1285–9.

    Article  CAS  PubMed  Google Scholar 

  109. Yiannakou Y, Piessevaux H, Bouchoucha M, Schiefke I, Filip R, Gabalec L, et al. A randomized, double-blind, placebo-controlled, phase 3 trial to evaluate the efficacy, safety, and tolerability of prucalopride in men with chronic constipation. Am J Gastroenterol. 2015;110:741–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Piessevaux H, Corazziari E, Rey E, Simren M, Wiechowska-Kozlowska A, Kerstens R, et al. A randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, and tolerability of long-term treatment with prucalopride. Neurogastroenterol Motil. 2015;27:805–15. No effects at 12 and 24 weeks.

    Article  CAS  PubMed  Google Scholar 

  111. • Ke M, Tack J, Quigley EM, Zou D, Choi SC, Leelakusolvong S, et al. Effect of prucalopride in the treatment of chronic constipation in Asian and non-Asian women: a pooled analysis of 4 randomized, placebo-controlled studies. J Neurogastroenterol Motil. 2014;20:458–68. A pooled analysis of prucalopride studies to date.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Tack J, Quigley EMM, Camilleri M, et al. Efficacy and safety of oral prucalopride in women with chronic constipation in whom laxatives have failed: an integrated analysis. UEG J. 2013;1:48–9.

    Google Scholar 

  113. Manini ML, Camilleri M, Goldberg M, et al. Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil. 2010;22:42–9.

    CAS  PubMed  Google Scholar 

  114. Goldberg M, Li YP, Johanson JF, et al. Clinical trial: the efficacy and tolerability of velusetrag, a selective 5-HT4 agonist with high intrinsic activity, in chronic idiopathic constipation—a 4-week, randomized, double-blind, placebo-controlled, dose-response study. Aliment Pharmacol Ther. 2010;32:1102–12.

    Article  CAS  PubMed  Google Scholar 

  115. Palme M, Milner PG, Ellis DJ, et al. A novel gastrointestinal prokinetic, ATI-7505, increased spontaneous bowel movements (SBMs) in a phase II, randomized, placebo-controlled trial of patients with chronic idiopathic constipation (CIC). Gastroenterology. 2010;138:S128–9.

    Article  Google Scholar 

  116. • Shin A, Camilleri M, Kolar G, Erwin P, West CP, Murad MH. Systematic review with meta-analysis: highly selective 5-HT4 agonists (prucalopride, velusetrag or naronapride) in chronic constipation. Aliment Pharmacol Ther. 2014;39:239–53. Provides a thorough and very helpful summary of the efficacy of the “new” prokinetics in constipation.

    Article  CAS  PubMed  Google Scholar 

  117. Tack J, Rotondo A, Meulemans A, Thielemans L, Cools M. Randomized clinical trial: a controlled pilot trial of the 5-HT4 receptor agonist revexepride in patients with symptoms suggestive of gastroparesis. Neurogastroenterol Motil. 2016;28:487–97.

    Article  CAS  PubMed  Google Scholar 

  118. Shaheen NJ, Adler J, Dedrie S, Johnson D, Malfertheiner P, Miner P, et al. Randomised clinical trial: the 5-HT4 agonist revexepride in patients with gastro-oesophageal reflux disease who have persistent symptoms despite PPI therapy. Aliment Pharmacol Ther. 2015;41:649–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Tack J, Zerbib F, Blondeau K, des Varannes SB, Piessevaux H, Borovicka J, et al. Randomized clinical trial: effect of the 5-HT4 receptor agonist revexepride on reflux parameters in patients with persistent reflux symptoms despite PPI treatment. Neurogastroenterol Motil. 2015;27:258–68.

    Article  CAS  PubMed  Google Scholar 

  120. Yoshida N, Omoya H, Oka M, Furukawa K, Ito T, Karasawa T. AS-4370, a novel gastrokinetic agent free of dopamine D2 receptor antagonist properties. Arch Int Pharmacodyn Ther. 1989;300:51–67.

    CAS  PubMed  Google Scholar 

  121. Asakawa H, Hayashi I, Fukui T, Tokunaga K. Effect of mosapride on glycemic control and gastric emptying in type 2 diabetes mellitus patients with gastropathy. Diabetes Res Clin Pract. 2003;61:175–82.

    Article  CAS  PubMed  Google Scholar 

  122. Amano T, Ariga H, Kurematsu A, Yamato S, Morioka S, Masaka A, et al. Effect of 5-hydroxytryptamine receptor 4 agonist mosapride on human gastric accommodation. Neurogastroenterol Motil. 2015;27:1303–9.

    Article  CAS  PubMed  Google Scholar 

  123. Hallerback BI, Bommelaer G, Bredberg E, Campbell M, Hellblom M, Lauritsen K, et al. Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study. Aliment Pharmacol Ther. 2002;16:959–67.

    Article  CAS  PubMed  Google Scholar 

  124. Amarapurkar DN, Rane P. Randomised, double-blind, comparative study to evaluate the efficacy and safety of ganaton (itopride hydrochloride) and mosapride citrate in the management of functional dyspepsia. J Indian Med Assoc. 2004;102:735–7.

    PubMed  Google Scholar 

  125. Otaka M, Jin M, Odashima M, Matsuhashi T, Wada I, Horikawa Y, et al. New strategy of therapy for functional dyspepsia using famotidine, mosapride and amitriptyline. Aliment Pharmacol Ther. 2005;21(Suppl 2):42–6.

    Article  CAS  PubMed  Google Scholar 

  126. Kinoshita Y, Hashimoto T, Kawamura A, Yuki M, Amano K, Sato H, et al. Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia. Aliment Pharmacol Ther. 2005;21(Suppl 2):37–41.

    Article  CAS  PubMed  Google Scholar 

  127. Seno H, Nakase H, Chiba T. Usefulness of famotidine in functional dyspepsia patient treatment: comparison among prokinetic, acid suppression and antianxiety therapies. Aliment Pharmacol Ther. 2005;21(Suppl 2):32–6.

    Article  CAS  PubMed  Google Scholar 

  128. Koshiyama H, Shimono D, Wada Y, Nakamura Y. Improvement of glycemic control after treatment with mosapride for diabetic gastropathy. Diabetes Care. 2000;23:1198–9.

    Article  CAS  PubMed  Google Scholar 

  129. Liu Z, Sakakibara R, Odaka T, Uchiyama T, Yamamoto T, Ito T, et al. Mosapride citrate, a novel 5-HT4 agonist and partial 5-HT3 antagonist, ameliorates constipation in Parkinsonian patients. Mov Disord. 2005;20:680–6.

    Article  PubMed  Google Scholar 

  130. Zhuang ZH, Zou FM, Tang DP, Zhuang JY, Wei JJ, Yang LY. The 5-HT4 receptor agonist mosapride attenuates inflammation of reflux esophagitis. Hepato-Gastroenterology. 2014;61:115–9.

    CAS  PubMed  Google Scholar 

  131. Lee MJ, Cho KH, Park HM, Sung HJ, Choi S, Im W. Pharmacological profile of DA-6886, a novel 5-HT4 receptor agonist to accelerate colonic motor activity in mice. Eur J Pharmacol. 2014;735:115–22.

    Article  CAS  PubMed  Google Scholar 

  132. Gilet M, Eutamene H, Han H, Kim HW, Bueno L. Influence of a new 5-HT4 receptor partial agonist, YKP10811, on visceral hypersensitivity in rats triggered by stress and inflammation. Neurogastroenterol Motil. 2014;26:1761–70.

    Article  CAS  PubMed  Google Scholar 

  133. Shin A, Acosta A, Camilleri M, Boldingh A, Burton D, Ryks M, et al. A randomized trial of 5-hydroxytryptamine4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation. Clin Gastroenterol Hepatol. 2015;13:701–8.

    Article  CAS  PubMed  Google Scholar 

  134. Camilleri M. The current role of erythromycin in the clinical management of gastric emptying disorders. Am J Gastroenterol. 1993;88:169.

    CAS  PubMed  Google Scholar 

  135. Jones KL, Berry M, Kong MF, et al. Hyperglycemia attenuates the gastrokinetic effect of erythromycin and affects the perception of post-prandial hunger in normal subjects. Diabetes Care. 1999;22:339.

    Article  CAS  PubMed  Google Scholar 

  136. Dhir R, Richter JE. Erythromycin in the short-and long-term control of dyspepsia symptoms in patients with gastroparesis. J Clin Gastroenterol. 2004;38:237.

    Article  CAS  PubMed  Google Scholar 

  137. Richards RD, Davenport K, McCallum RW. The treatment of idiopathic and diabetic gastroparesis with acute intravenous and chronic oral erythromycin. Am J Gastroenterol. 1993;88:203.

    CAS  PubMed  Google Scholar 

  138. Maganti K, Onyemere K, Jones MP. Oral erythromycin and symptomatic relief of gastroparesis: a systematic review. Am J Gastroenterol. 2003;98:259.

    CAS  PubMed  Google Scholar 

  139. Petrakis IE, Vrachassotakis N, Sciacca V, et al. Hyperglycemia attenuates erythromycin-induced acceleration of solid-phase gastric emptying in idiopathic and diabetic gastroparesis. Scand J Gastroenterol. 1999;34:396.

    Article  CAS  PubMed  Google Scholar 

  140. Brand RM, Lof J, Quigley EMM. Transdermal delivery of erythromcyin lactobionate—implications for the therapy of gastroparesis. Aliment Pharmacol Ther. 1997;11:589.

    Article  CAS  PubMed  Google Scholar 

  141. DiBiase JK, Quigley EMM. Efficacy of long-term intravenous erythromycin in the treatment of severe gastroparesis: one center’s experience. J Clin Gastroenterol. 1999;28:131.

    Article  Google Scholar 

  142. Larson JM, Tavakkoli A, Drane WE, Toskes PP, Moshiree B. Advantages of azithromycin over erythromycin in improving the gastric emptying half-time in adult patients with gastroparesis. J Neurogastroenterol Motil. 2010;16:407–13.

    Article  PubMed  PubMed Central  Google Scholar 

  143. Chini P, Toskes PP, Waseem S, Hou W, McDonald R, Moshiree B. Effect of azithromycin on small bowel motility in patients with gastrointestinal dysmotility. Scand J Gastroenterol. 2012;47:422–7.

    Article  CAS  PubMed  Google Scholar 

  144. Tack J, Peeters T. What comes after macrolides and other motilin stimulants? Gut. 2001;49:395–401.

    Article  Google Scholar 

  145. Sanger GJ, Westaway SM, Barnes AA, Macpherson DT, Muir AI, Jarvie EM, et al. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility. Neurogastroenterol Motil. 2009;21:657–64.

    Article  CAS  PubMed  Google Scholar 

  146. Hobson R, Farmer AD, Dewit OE, O’Donnell M, Hacquoil K, Robertson D, et al. The effects of camicinal, a novel motilin agonist, on gastro-esophageal function in healthy humans-a randomized placebo controlled trial. Neurogastroenterol Motil. 2015;27:1629–37.

    Article  CAS  PubMed  Google Scholar 

  147. • Chapman MJ, Deane AM, O’Connor SL, Nguyen NQ, Fraser RJ, Richards DB, et al. The effect of camicinal (GSK962040), a motilin agonist, on gastric emptying and glucose absorption in feed-intolerant critically ill patients: a randomized, blinded, placebo-controlled, clinical trial. Crit Care. 2016;20:232. Promising findings with a novel, highly selective motilin agonist in an important and much neglected clinical setting.

    Article  PubMed  PubMed Central  Google Scholar 

  148. Camilleri M, Acosta A. A ghrelin agonist fails to show benefit in patients with diabetic gastroparesis: let’s not throw the baby out with the bath water. Neurogastroenterol Motil. 2013;25:859–63.

    Article  CAS  PubMed  Google Scholar 

  149. Ejskjaer N, Vestergaard ET, Hellström PM, Gormsen LC, Madsbad S, Madsen JL, et al. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis. Aliment Pharmacol Ther. 2009;29:1179–87.

    Article  CAS  PubMed  Google Scholar 

  150. Pustovit RV, Callaghan B, Kosari S, Rivera LR, Thomas H, Brock JA, et al. The mechanism of enhanced defecation caused by the ghrelin receptor agonist, ulimorelin. Neurogastroenterol Motil. 2014;26:264–71.

    Article  CAS  PubMed  Google Scholar 

  151. •• Camilleri M, Acosta A. Emerging treatments in neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist. Neurogastroenterol Motil. 2015;27:324–32. Concise summary of a new and promising compound.

    Article  CAS  PubMed  Google Scholar 

  152. Ejskjaer N, Dimcevski G, Wo J, Hellström PM, Gormsen LC, Sarosiek I, et al. Safety and efficacy of ghrelin agonist TZP-101 in relieving symptoms in patients with diabetic gastroparesis: a randomized, placebo-controlled study. Neurogastroenterol Motil. 2010;22:1069–e281.

    Article  CAS  PubMed  Google Scholar 

  153. Wo JM, Ejskjaer N, Hellström PM, Malik RA, Pezzullo JC, Shaughnessy L, et al. Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting--randomised clinical study subset data. Aliment Pharmacol Ther. 2011;33:679–88.

    Article  CAS  PubMed  Google Scholar 

  154. Popescu I, Fleshner PR, Pezzullo JC, Charlton PA, Kosutic G, Senagore AJ. The ghrelin agonist TZP-101 for management of postoperative ileus after partial colectomy: a randomized, dose-ranging, placebo-controlled clinical trial. Dis Colon Rectum. 2010;53:126–34.

    Article  PubMed  Google Scholar 

  155. Bochicchio G, Charlton P, Pezzullo JC, Kosutic G, Senagore A. Ghrelin agonist TZP-101/ulimorelin accelerates gastrointestinal recovery independently of opioid use and surgery type: covariate analysis of phase 2 data. World J Surg. 2012;36:39–45.

    Article  PubMed  Google Scholar 

  156. Shaw M, Pediconi C, McVey D, Mondou E, Quinn J, Chamblin B, et al. Safety and efficacy of ulimorelin administered postoperatively to accelerate recovery of gastrointestinal motility following partial bowel resection: results of two randomized, placebo-controlled phase 3 trials. Dis Colon Rectum. 2013;56:888–97.

    Article  PubMed  Google Scholar 

  157. Ejskjaer N, Wo JM, Esfandyari T, Mazen Jamal M, Dimcevski G, Tarnow L, et al. A phase 2a, randomized, double-blind 28-day study of TZP-102 a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013;25:e140–50.

    Article  CAS  PubMed  Google Scholar 

  158. McCallum RW, Lembo A, Esfandyari T, Bhandari BR, Ejskjaer N, Cosentino C, et al. Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis. Neurogastroenterol Motil. 2013;25:e705–17.

    Article  CAS  PubMed  Google Scholar 

  159. Nelson AD, Camilleri M, Acosta A, Busciglio I, Linker Nord S, Boldingh A, et al. Effects of ghrelin receptor agonist, relamorelin, on gastric motor functions and satiation in healthy volunteers. Neurogastroenterol Motil. 2016;28:1705–13.

    Article  CAS  PubMed  Google Scholar 

  160. Acosta A, Camilleri M, Busciglio I, Boldingh A, Nelson AD, Burton D. Short-term effects of relamorelin on descending colon motility in chronic constipation: a randomized, controlled trial. Dig Dis Sci. 2016;61:852–60.

    Article  CAS  PubMed  Google Scholar 

  161. Shin A, Camilleri M, Busciglio I, Burton D, Smith SA, Vella A, et al. The ghrelin agonist RM-131 accelerates gastric emptying of solids and reduces symptoms in patients with type 1 diabetes mellitus. Clin Gastroenterol Hepatol. 2013;11:1453–1459.e4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Shin A, Camilleri M, Busciglio I, Burton D, Stoner E, Noonan P, et al. Randomized controlled phase Ib study of ghrelin agonist, RM-131, in type 2 diabetic women with delayed gastric emptying: pharmacokinetics and pharmacodynamics. Diabetes Care. 2013;36:41–8.

    Article  CAS  PubMed  Google Scholar 

  163. • Lembo A, Camilleri M, McCallum R, Sastre R, Breton C, Spence S, et al. Relamorelin reduces vomiting frequency and severity and accelerates gastric emptying in adults with diabetic gastroparesis. Gastroenterology. 2016;151:87–96. Very promising results in a challenging disorder.

    Article  CAS  PubMed  Google Scholar 

  164. • Acosta A, Camilleri M, Kolar G, Iturrino J, Szarka LA, Boldingh A, et al. Relamorelin relieves constipation and accelerates colonic transit in a phase 2, placebo-controlled, randomized trial. Clin Gastroenterol Hepatol. 2015;13:2312–9. A parenteral drug for constipation?

    Article  CAS  PubMed  Google Scholar 

  165. Callaghan B, Kosari S, Pustovit RV, Sartor DM, Ferens D, Ban K, et al. Hypotensive effects of ghrelin receptor agonists mediated through a novel receptor. Br J Pharmacol. 2014;171:1275–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  166. Mosińska P, Zatorski H, Storr M, Fichna J. Future treatment of constipation-associated disorders: role of relamorelin and other ghrelin receptor agonists. J Neurogastroenterol Motil. 2017;23:171–9.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Lynda K and David M Underwood Center for Digestive Disorders, Houston, TX, USA

    Eamonn M. M. Quigley

  2. Division of Gastroenterology and Hepatology, The Methodist Hospital, 6550 Fannin St, SM 1201, Houston, TX, 77030, USA

    Eamonn M. M. Quigley

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Quigley, E.M.M. Prokinetics in the Management of Functional Gastrointestinal Disorders. Curr Gastroenterol Rep 19, 53 (2017). https://doi.org/10.1007/s11894-017-0593-6

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