{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T15:54:03Z","timestamp":1791906843613,"version":"4.3.4"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T00:00:00Z","timestamp":1629763200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Prokinetic agents amplify and coordinate the gastrointestinal muscular contractions to facilitate the transit of intra-luminal content. Following the institution of dietary recommendations, prokinetics are the first medications whose goal is to improve gastric emptying and relieve symptoms of gastroparesis. The recommended use of metoclopramide, the only currently approved medication for gastroparesis in the United States, is for a duration of less than 3\u00a0months, due to the risk of reversible or irreversible extrapyramidal tremors. Domperidone, a dopamine D2 receptor antagonist, is available for prescription through the FDA\u2019s program for Expanded Access to Investigational Drugs. Macrolides are used off label and are associated with tachyphylaxis and variable duration of efficacy. Aprepitant relieves some symptoms of gastroparesis. There are newer agents in the pipeline targeting diverse gastric (fundic, antral and pyloric) motor functions, including novel serotonergic 5-HT<jats:sub>4<\/jats:sub> agonists, dopaminergic D<jats:sub>2\/3<\/jats:sub> antagonists, neurokinin NK<jats:sub>1<\/jats:sub> antagonists, and ghrelin agonist. Novel targets with potential to improve gastric motor functions include the pylorus, macrophage\/inflammatory function, oxidative stress, and neurogenesis. In the current review, we discuss the use of pharmacological approaches with potential to enhance motor functions in the management of gastroparesis.<\/jats:p>","DOI":"10.3389\/fphar.2021.711500","type":"journal-article","created":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:53:41Z","timestamp":1629780821000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":98,"title":["New Developments in Prokinetic Therapy for Gastric Motility Disorders"],"prefix":"10.3389","volume":"12","author":[{"given":"Michael","family":"Camilleri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Atieh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"616","DOI":"10.1007\/bf01297028","article-title":"Long-term Efficacy of Oral Cisapride in Symptomatic Upper Gut Dysmotility","volume":"36","author":"Abell","year":"1991","journal-title":"Dig. Dis. Sci."},{"key":"B2","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1016\/j.gtc.2014.11.008","article-title":"Prokinetics in Gastroparesis","volume":"44","author":"Acosta","year":"2015","journal-title":"Gastroenterol. Clin. North. Am."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1251","DOI":"10.1111\/j.1365-2036.2007.03467.x","article-title":"Clinical Trial: a Randomized-Controlled Crossover Study of Intrapyloric Injection of Botulinum Toxin in Gastroparesis","volume":"26","author":"Arts","year":"2007","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B4","first-page":"468","article-title":"A Double-Blind Comparison of Clebopride and Placebo in Dyspepsia Secondary to Delayed Gastric Emptying","volume":"7","author":"Bavestrello","year":"1985","journal-title":"Clin. Ther."},{"key":"B5","doi-asserted-by":"publisher","first-page":"25","DOI":"10.3389\/fphar.2011.00025","article-title":"The Pharmacology of TD-8954, a Potent and Selective 5-HT(4) Receptor Agonist with Gastrointestinal Prokinetic Properties","volume":"2","author":"Beattie","year":"2011","journal-title":"Front. Pharmacol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.vph.2012.11.002","article-title":"An In Vitro Investigation of the Cardiovascular Effects of the 5-HT(4) Receptor Selective Agonists, Velusetrag and TD-8954","volume":"58","author":"Beattie","year":"2013","journal-title":"Vascul Pharmacol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1111\/nmo.12389","article-title":"Association of Low Numbers of CD206-Positive Cells with Loss of ICC in the Gastric Body of Patients with Diabetic Gastroparesis","volume":"26","author":"Bernard","year":"2014","journal-title":"Neurogastroenterol Motil."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1111\/nmo.12874","article-title":"Effects of Hemin on Heme Oxygenase-1, Gastric Emptying, and Symptoms in Diabetic Gastroparesis","volume":"28","author":"Bharucha","year":"2016","journal-title":"Neurogastroenterol Motil."},{"key":"B9","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1159\/000201227","article-title":"Comparison between the Effects of Neostigmine and Ranitidine on Interdigestive Gastroduodenal Motility of Patients with Gastroparesis","volume":"56","author":"Bortolotti","year":"1995","journal-title":"Digestion"},{"key":"B10","doi-asserted-by":"publisher","first-page":"2439","DOI":"10.1023\/a:1026674719476","article-title":"Effect of Intravenous Clarithromycin on Interdigestive Gastroduodenal Motility of Patients with Functional Dyspepsia and Helicobacter pylori Gastritis","volume":"44","author":"Bortolotti","year":"1999","journal-title":"Dig. Dis. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.3389\/fimmu.2017.01873","article-title":"Cholinergic Modulation of Type 2 Immune Responses","volume":"8","author":"Bosmans","year":"2017","journal-title":"Front. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1136\/gut.51.6.781","article-title":"SPECT Imaging of the Stomach: Comparison with Barostat, and Effects of Sex, Age, Body Mass index, and Fundoplication. Single Photon Emission Computed Tomography","volume":"51","author":"Bouras","year":"2002","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","first-page":"1341","DOI":"10.1046\/j.1365-2036.2002.01257.x","article-title":"Long-term Cisapride Treatment Improves Diabetic Gastroparesis but Not Glycaemic Control","volume":"16","author":"Braden","year":"2002","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1111\/j.1365-2982.2012.01972.x","article-title":"Performance Characteristics of Scintigraphic Measurement of Gastric Emptying of Solids in Healthy Participants","volume":"24","author":"Camilleri","year":"2012","journal-title":"Neurogastroenterol Motil."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1139","DOI":"10.1111\/apt.15711","article-title":"Overall Safety of Relamorelin in Adults with Diabetic Gastroparesis: Analysis of Phase 2a and 2b Trial Data","volume":"51","author":"Camilleri","year":"2020","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B16","doi-asserted-by":"publisher","first-page":"704","DOI":"10.1016\/0016-5085(89)90893-7","article-title":"Effect of Six Weeks of Treatment with Cisapride in Gastroparesis and Intestinal Pseudoobstruction","volume":"96","author":"Camilleri","year":"1989","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1240","DOI":"10.1053\/j.gastro.2017.07.035","article-title":"Efficacy and Safety of Relamorelin in Diabetics with Symptoms of Gastroparesis: a Randomized, Placebo-Controlled Study","volume":"153","author":"Camilleri","year":"2017","journal-title":"Gastroenterology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1038\/nrgastro.2009.72","article-title":"Actions and Therapeutic Pathways of Ghrelin for Gastrointestinal Disorders","volume":"6","author":"Camilleri","year":"2009","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/ajg.2012.373","article-title":"Clinical Guideline: Management of Gastroparesis","volume":"108","author":"Camilleri","year":"2013","journal-title":"Am. J. Gastroenterol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1053\/j.gastro.2020.04.072","article-title":"Opiates, the Pylorus and Gastroparesis","volume":"159","author":"Camilleri","year":"2020","journal-title":"Gastroenterology"},{"key":"B21","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1097\/mpg.0000000000001386","article-title":"The Intragastric Pressure Measurement: A Novel Method to Assess Gastric Accommodation in Functional Dyspepsia Children","volume":"64","author":"Carbone","year":"2017","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.14309\/ajg.0000000000000304","article-title":"Prucalopride in Gastroparesis: a Randomized Placebo-Controlled Crossover Study","volume":"114","author":"Carbone","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1053\/j.gastro.2020.07.029","article-title":"Efficacy and Safety of Tradipitant in Patients with Diabetic and Idiopathic Gastroparesis in a Randomized, Placebo-Controlled Trial","volume":"160","author":"Carlin","year":"2021","journal-title":"Gastroenterology"},{"key":"B24","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1136\/gut.33.3.397","article-title":"Erythromycin and the Gut","volume":"33","author":"Catnach","year":"1992","journal-title":"Gut"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.3748\/wjg.v9.i8.187710.3748\/wjg.v9.i8.1874","article-title":"Effects of Neurotrophins on Gastrointestinal Myoelectric Activities of Rats","volume":"9","author":"Chai","year":"2003","journal-title":"World J. Gastroenterol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/jpen.1732","article-title":"Blinded, Double\u2010Dummy, Parallel\u2010Group, Phase 2a Randomized Clinical Trial to Evaluate the Efficacy and Safety of a Highly Selective 5\u2010Hydroxytryptamine Type 4 Receptor Agonist in Critically Ill Patients with Enteral Feeding Intolerance","volume":"45","author":"Chapman","year":"2021","journal-title":"J. Parenter. Enteral Nutr."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1111\/apt.16304","article-title":"Randomised Study: Effects of the 5-HT4 Receptor Agonist Felcisetrag vs Placebo on Gut Transit in Patients with Gastroparesis","volume":"53","author":"Chedid","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B28","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1038\/s41395-018-0234-1","article-title":"Characterization of Upper Gastrointestinal Symptoms, Gastric Motor Functions, and Associations in Patients with Diabetes at a Referral center","volume":"114","author":"Chedid","year":"2019","journal-title":"Am. J. Gastroenterol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"e13581","DOI":"10.1111\/nmo.13581","article-title":"Gastric Accommodation Measurements by Single Photon Emission Computed Tomography and Two-Dimensional Scintigraphy in Diabetic Patients with Upper Gastrointestinal Symptoms","volume":"31","author":"Chedid","year":"2019","journal-title":"Neurogastroenterol Motil."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1053\/j.gastro.2008.09.003","article-title":"Heme Oxygenase-1 Protects Interstitial Cells of Cajal from Oxidative Stress and Reverses Diabetic Gastroparesis","volume":"135","author":"Choi","year":"2008","journal-title":"Gastroenterology"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2122","DOI":"10.1053\/j.gastro.2018.02.027","article-title":"Change in Populations of Macrophages Promotes Development of Delayed Gastric Emptying in Mice","volume":"154","author":"Cipriani","year":"2018","journal-title":"Gastroenterology"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2634","DOI":"10.1007\/s10620-008-0660-9","article-title":"Factors Associated with Symptom Response to Pyloric Injection of Botulinum Toxin in a Large Series of Gastroparesis Patients","volume":"54","author":"Coleski","year":"2009","journal-title":"Dig. Dis. Sci."},{"key":"B33","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1136\/gut.28.3.300","article-title":"Effect of Chronic Administration of Cisapride on Gastric Emptying of a Solid Meal and on Dyspeptic Symptoms in Patients with Idiopathic Gastroparesis","volume":"28","author":"Corinaldesi","year":"1987","journal-title":"Gut"},{"key":"B34","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1053\/gast.2000.8553","article-title":"Recombinant Human Neurotrophic Factors Accelerate Colonic Transit and Relieve Constipation in Humans","volume":"119","author":"Coulie","year":"2000","journal-title":"Gastroenterology"},{"key":"B35","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1136\/gut.43.3.395","article-title":"Involvement of Two Different Pathways in the Motor Effects of Erythromycin on the Gastric Antrum in Humans","volume":"43","author":"Coulie","year":"1998","journal-title":"Gut"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5798","DOI":"10.1073\/pnas.1720267115","article-title":"Estrogen Receptor \u03b2 Controls Proliferation of Enteric Glia and Differentiation of Neurons in the Myenteric Plexus after Damage","volume":"115","author":"D'Errico","year":"2018","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B37","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1124\/jpet.106.101329","article-title":"Differential Effects of 5-hydroxytryptamine4 Receptor Agonists at Gastric versus Cardiac Receptors: an Operational Framework to Explain and Quantify Organ-specific Behavior","volume":"317","author":"De Maeyer","year":"2006","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B38","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2018.07.048","article-title":"Self-maintaining Gut Macrophages Are Essential for Intestinal Homeostasis","volume":"175","author":"De Schepper","year":"2018","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1016\/j.clpt.2004.04.012","article-title":"The Effect of Sildenafil on Gastric Emptying in Patients with End-Stage Renal Failure and Symptoms of Gastroparesis","volume":"76","author":"Dishy","year":"2004","journal-title":"Clin. Pharmacol. Ther."},{"key":"B40","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1111\/j.1572-0241.2007.01676.x","article-title":"Botulinum Toxin A for the Treatment of Delayed Gastric Emptying","volume":"103","author":"Friedenberg","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1053\/j.gastro.2005.12.026","article-title":"Brain-derived Neurotrophic Factor Augments Peristalsis by Augmenting 5-HT and Calcitonin Gene-Related Peptide Release","volume":"130","author":"Grider","year":"2006","journal-title":"Gastroenterology"},{"key":"B42","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1111\/j.1365-2982.2012.01894.x","article-title":"Clinical-histological Associations in Gastroparesis: Results from the Gastroparesis Clinical Research Consortium","volume":"24","author":"Grover","year":"2012","journal-title":"Neurogastroenterol Motil."},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1111\/nmo.13018","article-title":"Diabetic and Idiopathic Gastroparesis Is Associated with Loss of CD206-Positive Macrophages in the Gastric Antrum","volume":"29","author":"Grover","year":"2017","journal-title":"Neurogastroenterol Motil."},{"key":"B44","doi-asserted-by":"publisher","first-page":"1575","DOI":"10.1053\/j.gastro.2011.01.046","article-title":"Cellular Changes in Diabetic and Idiopathic Gastroparesis","volume":"140","author":"Grover","year":"2011","journal-title":"Gastroenterology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"e13298","DOI":"10.1111\/nmo.13298","article-title":"Effects of Naloxegol on Whole Gut Transit in Opioid-Na\u00efve Healthy Subjects Receiving Codeine: A Randomized, Controlled Trial","volume":"30","author":"Halawi","year":"2018","journal-title":"Neurogastroenterol Motil."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1016\/j.cgh.2018.10.013","article-title":"Opioid Use and Potency Are Associated with Clinical Features, Quality of Life, and Use of Resources in Patients with Gastroparesis","volume":"17","author":"Hasler","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e13230","DOI":"10.1111\/nmo.13230","article-title":"Idiopathic Gastroparesis Is Associated with Specific Transcriptional Changes in the Gastric Muscularis Externa","volume":"30","author":"Herring","year":"2018","journal-title":"Neurogastroenterol Motil."},{"key":"B48","doi-asserted-by":"publisher","first-page":"G505","DOI":"10.1152\/ajpgi.00197.2017","article-title":"Effects of NK1 Receptors on Gastric Motor Functions and Satiation in Healthy Humans: Results from a Controlled Trial with the NK1 Antagonist Aprepitant","volume":"313","author":"Jacob","year":"2017","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1028","DOI":"10.1056\/nejm199004123221502","article-title":"Improvement of Gastric Emptying in Diabetic Gastroparesis by Erythromycin. Preliminary Studies","volume":"322","author":"Janssens","year":"1990","journal-title":"N. Engl. J. Med."},{"key":"B50","doi-asserted-by":"publisher","first-page":"1510","DOI":"10.1007\/s10620-012-2085-8","article-title":"Effect of Mosapride Citrate on Gastric Emptying in Interferon-Induced Gastroparesis","volume":"57","author":"Kawamura","year":"2012","journal-title":"Dig. Dis. Sci."},{"key":"B51","doi-asserted-by":"publisher","first-page":"E3709","DOI":"10.1073\/pnas.1619406114","article-title":"Adult Enteric Nervous System in Health Is Maintained by a Dynamic Balance between Neuronal Apoptosis and Neurogenesis","volume":"114","author":"Kulkarni","year":"2017","journal-title":"Proc. Natl. Acad. Sci. U S A."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1111\/apt.16344","article-title":"Velusetrag Accelerates Gastric Emptying in Subjects with Gastroparesis: a Multicentre, Double-Blind, Randomised, Placebo-Controlled, Phase 2 Study","volume":"53","author":"Kuo","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B53","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1111\/apt.16451","article-title":"Randomised Clinical Trial: Safety, Pharmacokinetics and Pharmacodynamics of Trazpiroben (TAK\u2010906), a Dopamine D 2\/D 3 Receptor Antagonist, in Patients with Gastroparesis","volume":"54","author":"Kuo","year":"2021","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B54","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1111\/j.1365-2982.2012.01897.x","article-title":"Therapeutic Efficacy of Acotiamide in Patients with Functional Dyspepsia Based on Enhanced Postprandial Gastric Accommodation and Emptying: Randomized Controlled Study Evaluation by Real-Time Ultrasonography","volume":"24","author":"Kusunoki","year":"2012","journal-title":"Neurogastroenterol Motil."},{"key":"B55","doi-asserted-by":"publisher","first-page":"407","DOI":"10.5056\/jnm.2010.16.4.407","article-title":"Advantages of Azithromycin over Erythromycin in Improving the Gastric Emptying Half-Time in Adult Patients with Gastroparesis","volume":"16","author":"Larson","year":"2010","journal-title":"J. Neurogastroenterol Motil."},{"key":"B56","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1053\/j.gastro.2016.03.038","article-title":"Relamorelin Reduces Vomiting Frequency and Severity and Accelerates Gastric Emptying in Adults with Diabetic Gastroparesis","volume":"151","author":"Lembo","year":"2016","journal-title":"Gastroenterology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1046\/j.1365-2982.2001.00287.x","article-title":"Pharmacological Modulation of Human Gastric Volumes Demonstrated Noninvasively Using SPECT Imaging","volume":"13","author":"Liau","year":"2001","journal-title":"Neurogastroenterol Motil."},{"key":"B58","first-page":"14","article-title":"Does Neostigmine Increase Gastric Emptying in the Critically Ill?-Rresults of a Pilot Study","volume":"5","author":"Lucey","year":"2003","journal-title":"Crit. Care Resusc"},{"key":"B59","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1007\/s40272-017-0277-6","article-title":"Application of Pyridostigmine in Pediatric Gastrointestinal Motility Disorders: a Case Series","volume":"20","author":"Manini","year":"2017","journal-title":"Paediatr. Drugs"},{"key":"B60","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1136\/gutjnl-2011-301454","article-title":"A Placebo-Controlled Trial of Acotiamide for Meal-Related Symptoms of Functional Dyspepsia","volume":"61","author":"Matsueda","year":"2012","journal-title":"Gut"},{"key":"B61","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1136\/gutjnl-2013-304676","article-title":"A Distinct Vagal Anti-inflammatory Pathway Modulates Intestinal Muscularis Resident Macrophages Independent of the Spleen","volume":"63","author":"Matteoli","year":"2013","journal-title":"Gut"},{"key":"B62","doi-asserted-by":"publisher","first-page":"1919","DOI":"10.1016\/0016-5085(86)90262-3","article-title":"Pyloric Dysfunction in Diabetics with Recurrent Nausea and Vomiting","volume":"90","author":"Mearin","year":"1986","journal-title":"Gastroenterology"},{"key":"B63","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1001\/archinte.1986.00360160140019","article-title":"Functional Dyspepsia and Chronic Idiopathic Gastric Stasis. Role of Endogenous Opiates","volume":"146","author":"Narducci","year":"1986","journal-title":"Arch. Intern. Med."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1705","DOI":"10.1111\/nmo.12870","article-title":"Effects of Ghrelin Receptor Agonist, Relamorelin, on Gastric Motor Functions and Satiation in Healthy Volunteers","volume":"28","author":"Nelson","year":"2016","journal-title":"Neurogastroenterol Motil."},{"key":"B65","doi-asserted-by":"publisher","first-page":"138","DOI":"10.2967\/jnmt.118.215566","article-title":"Enhanced Gastric Emptying Scintigraphy to Assess Fundic Accommodation Using Intragastric Meal Distribution and Antral Contractility","volume":"47","author":"Orthey","year":"2018","journal-title":"J. Nucl. Med. Technol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"691","DOI":"10.2967\/jnumed.117.197053","article-title":"Intragastric Meal Distribution during Gastric Emptying Scintigraphy for Assessment of Fundic Accommodation: Correlation with Symptoms of Gastroparesis","volume":"59","author":"Orthey","year":"2018","journal-title":"J. Nucl. Med."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1689","DOI":"10.1038\/ajg.2017.264","article-title":"Gastric Motor Dysfunction in Patients with Functional Gastroduodenal Symptoms","volume":"112","author":"Park","year":"2017","journal-title":"Am. J. Gastroenterol."},{"key":"B68","doi-asserted-by":"publisher","first-page":"G418","DOI":"10.1152\/ajpgi.1995.269.3.g418","article-title":"Gastrokinetic Effects of Erythromycin: Myogenic and Neurogenic Mechanisms of Action in Rabbit Stomach","volume":"269","author":"Parkman","year":"1995","journal-title":"Am. J. Physiol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1053\/j.gastro.2017.08.033","article-title":"Aprepitant Has Mixed Effects on Nausea and Reduces Other Symptoms in Patients with Gastroparesis and Related Disorders","volume":"154","author":"Pasricha","year":"2018","journal-title":"Gastroenterology"},{"key":"B70","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/j.1572-0241.1999.00456.x","article-title":"A Double-Blind Multicenter Comparison of Domperidone and Metoclopramide in the Treatment of Diabetic Patients with Symptoms of Gastroparesis","volume":"94","author":"Patterson","year":"1999","journal-title":"Am. J. Gastroenterol."},{"key":"B71","first-page":"95","article-title":"Central and Peripheral Mechanisms by Which Ghrelin Regulates Gut Motility","author":"Peeters","year":"2003","journal-title":"J. Physiol. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1016\/j.gastrohep.2009.06.013","article-title":"Efficacy and Tolerability of Cinitapride in the Treatment of Functional Dyspepsia and Delayed Gastric Emptying","volume":"32","author":"Portincasa","year":"2009","journal-title":"Gastroenterol. Hepatol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1056\/nejmoa040582","article-title":"Oral Erythromycin and the Risk of Sudden Death from Cardiac Causes","volume":"351","author":"Ray","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"B74","first-page":"203","article-title":"The Treatment of Idiopathic and Diabetic Gastroparesis with Acute Intravenous and Chronic Oral Erythromycin","volume":"88","author":"Richards","year":"1993","journal-title":"Am. J. Gastroenterol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1007\/bf01295905","article-title":"Objective and Subjective Results of a Randomized, Double-Blind, Placebo-Controlled Trial Using Cisapride to Treat Gastroparesis","volume":"38","author":"Richards","year":"1993","journal-title":"Dig. Dis. Sci."},{"key":"B76","doi-asserted-by":"publisher","first-page":"1453","DOI":"10.1016\/j.cgh.2013.04.019","article-title":"The Ghrelin Agonist RM-131 Accelerates Gastric Emptying of Solids and Reduces Symptoms in Patients with Type 1 Diabetes Mellitus","volume":"11","author":"Shin","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"41","DOI":"10.2337\/dc12-1128","article-title":"Randomized Controlled Phase Ib Study of Ghrelin Agonist, RM-131, in Type 2 Diabetic Women with Delayed Gastric Emptying: Pharmacokinetics and Pharmacodynamics","volume":"36","author":"Shin","year":"2013","journal-title":"Diabetes Care"},{"key":"B78","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1136\/gutjnl-2018-317263","article-title":"Preoperative Administration of the 5-HT4 Receptor Agonist Prucalopride Reduces Intestinal Inflammation and Shortens Postoperative Ileus via Cholinergic Enteric Neurons","volume":"68","author":"Stakenborg","year":"2019","journal-title":"Gut"},{"key":"B79","doi-asserted-by":"publisher","first-page":"697","DOI":"10.1007\/bf02213125","article-title":"Antral Axial Forces Postprandially and after Erythromycin in Organic and Functional Dysmotilities","volume":"41","author":"Surrenti","year":"1996","journal-title":"Dig. Dis. Sci."},{"key":"B80","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1016\/j.cgh.2008.01.009","article-title":"A Stable Isotope Breath Test with a Standard Meal for Abnormal Gastric Emptying of Solids in the Clinic and in Research","volume":"6","author":"Szarka","year":"2008","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1136\/gut.52.9.1271","article-title":"Assessment of Meal Induced Gastric Accommodation by a Satiety Drinking Test in Health and in Severe Functional Dyspepsia","volume":"52","author":"Tack","year":"2003","journal-title":"Gut"},{"key":"B82","doi-asserted-by":"publisher","first-page":"745","DOI":"10.1111\/j.1365-2036.2012.05011.x","article-title":"Systematic Review: Cardiovascular Safety Profile of 5-HT(4) Agonists Developed for Gastrointestinal Disorders","volume":"35","author":"Tack","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B83","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1136\/gut.2004.060426","article-title":"Influence of Ghrelin on Interdigestive Gastrointestinal Motility in Humans","volume":"55","author":"Tack","year":"2006","journal-title":"Gut"},{"key":"B84","doi-asserted-by":"publisher","first-page":"e32","DOI":"10.1111\/j.1365-2982.2010.01613.x","article-title":"Influence of Tegaserod on Proximal Gastric Tone and on the Perception of Gastric Distention in Functional Dyspepsia","volume":"23","author":"Tack","year":"2010","journal-title":"Neurogastroenterol Motil."},{"key":"B85","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1016\/s0016-5085(98)70012-5","article-title":"Role of Impaired Gastric Accommodation to a Meal in Functional Dyspepsia","volume":"115","author":"Tack","year":"1998","journal-title":"Gastroenterology"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1124\/jpet.104.081497","article-title":"Desensitization of the Human Motilin Receptor by Motilides","volume":"313","author":"Thielemans","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B87","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1111\/j.1365-2036.2004.01867.x","article-title":"Review Article: Clinical Implications of Enteric and central D2 Receptor Blockade by Antidopaminergic Gastrointestinal Prokinetics","volume":"19","author":"Tonini","year":"2004","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1906","DOI":"10.1111\/j.1572-0241.2008.01953.x","article-title":"Tegaserod Treatment for Dysmotility-like Functional Dyspepsia: Results of Two Randomized, Controlled Trials","volume":"103","author":"Vakil","year":"2008","journal-title":"Am. J. Gastroenterol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.lfs.2014.06.003","article-title":"Preclinical Gastrointestinal Prokinetic Efficacy and Endocrine Effects of the Ghrelin Mimetic RM-131","volume":"109","author":"Van der Ploeg","year":"2014","journal-title":"Life Sci."},{"key":"B90","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1053\/j.gastro.2019.01.249","article-title":"Effects of Promotility Agents on Gastric Emptying and Symptoms: a Systematic Review and Meta-Analysis","volume":"156","author":"Vijayvargiya","year":"2019","journal-title":"Gastroenterology"},{"key":"B91","doi-asserted-by":"publisher","first-page":"1289","DOI":"10.1016\/j.gie.2020.01.044","article-title":"Role of Endoscopic Functional Luminal Imaging Probe in Predicting the Outcome of Gastric Peroral Endoscopic Pyloromyotomy (With Video)","volume":"91","author":"Vosoughi","year":"2020","journal-title":"Gastrointest. Endosc."},{"key":"B92","doi-asserted-by":"publisher","first-page":"G759","DOI":"10.1152\/ajpgi.00008.2021","article-title":"Gastric Accommodation Influences Proximal Gastric and Total Gastric Emptying in Concurrent Measurements Conducted in Healthy Volunteers","volume":"320","author":"Wang","year":"2021","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1172\/JCI8273","article-title":"Insulin Restores Neuronal Nitric Oxide Synthase Expression and Function that Is Lost in Diabetic Gastropathy","volume":"106","author":"Watkins","year":"2000","journal-title":"J. Clin. Invest."},{"key":"B94","doi-asserted-by":"publisher","first-page":"884","DOI":"10.1111\/j.1365-2036.2010.04422.x","article-title":"The Effects of Methylnaltrexone Alone and in Combination with Acutely Administered Codeine on Gastrointestinal and Colonic Transit in Health","volume":"32","author":"Wong","year":"2010","journal-title":"Aliment. Pharmacol. Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.711500\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,8,24]],"date-time":"2021-08-24T04:53:47Z","timestamp":1629780827000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2021.711500\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,24]]},"references-count":94,"alternative-id":["10.3389\/fphar.2021.711500"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2021.711500","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,24]]},"article-number":"711500"}}