Evolving pharmacological approaches in gastroesophageal reflux disease

Expert Opinion on Emerging Drugs

Volumn 17, Issue 3, 2012, Pages 347-359

  Altan, Ege ^a   Blondeau, Kathleen ^a   Pauwels, Ans ^a   Farré, Ricard ^a   Tack, Jan ^a  

^a UNIVERSITY OF LEUVEN   (Belgium)

Author keywords

Arbaclofen; Dexlansoprazole; Extended release rabeprazole; Gastroesophageal reflux disease; Immediate release omeprazole; Itopride; Mosapride; Potassium competitive acid blockers; Prokinetics; Proton pump inhibitors; Tenatoprazole; Transient lower esophageal sphincter relaxations

Indexed keywords

4 AMINOBUTYRIC ACID; ADX 10059; AGN 201904Z; ARBACLOFEN PLACARBIL; AZD 1386; BACLOFEN; BENATOPRAZOLE; CANNABINOID 1 RECEPTOR; CHINESE DRUG; DRONABINOL; ESOMEPRAZOLE; ITOPRIDE; LANSOPRAZOLE; LESOGABERAN; LINAPRAZAN; MOSAPRIDE; OMEPRAZOLE; PANTOPRAZOLE; PROTON PUMP INHIBITOR; RABEPRAZOLE; RIKKUNSHITO; RIMONABANT; TAK 438; UNCLASSIFIED DRUG; VB 101;

ACID SECRETION; CENTRAL NERVOUS SYSTEM; DRUG TARGETING; DRUG TOLERABILITY; DYSPEPSIA; ESOPHAGITIS; ESOPHAGUS MOTILITY; GASTROESOPHAGEAL REFLUX; HEALTH CARE NEED; HEARTBURN; HUMAN; LIVER TOXICITY; LOWER ESOPHAGUS SPHINCTER; PATIENT SELECTION; REVIEW; STOMACH PH; TREATMENT RESPONSE;

ANTACIDS; CLINICAL TRIALS AS TOPIC; ESOPHAGEAL MOTILITY DISORDERS; ESOPHAGEAL SPHINCTER, LOWER; GASTROESOPHAGEAL REFLUX; GASTROINTESTINAL MOTILITY; HUMANS; PROTON PUMP INHIBITORS; TREATMENT OUTCOME;

EID: 84865579774     PISSN: 14728214     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728214.2012.702753     Document Type: Review

References (113)

1. Dent J, El-Serag HB, Wallander MA, Johansson S. Epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut 2005;54(5):710-17 (Pubitemid 40559260)
2. Mittal RK, Holloway RH, Penagini R, et al. Transient lower esophageal sphincter relaxation. Gastroenterology 1995;109(2):601-10
3. Sifrim D, Holloway R, Silny J, et al. Composition of the postprandial refluxate in patients with gastroesophageal reflux disease. Am J Gastroenterol 2001;96(3):647-55 (Pubitemid 32240710)
4. Ang D, Blondeau K, Sifrim D, Tack J. The spectrum of motor function abnormalities in gastroesophageal reflux disease and Barrett's esophagus. Digestion 2009;79(3):158-68
5. Horn J. The proton-pump inhibitors: similarities and differences. Clin Ther 2000;22(3):266-80 (Pubitemid 30213134)
6. Howden CW. Appropriate acid suppression in the treatment of acid-related conditions. Pharmacol Ther 1994;63(1):123-34 (Pubitemid 24250151)
7. Guirguis-Blake J. Medical treatments in the short-term management of reflux esophagitis. Am Fam Physician 2008;77(5):620
8. Khan M, Santana J, Donnellan C, et al. Medical treatments in the short term management of reflux oesophagitis. Cochrane Database Syst Rev 2007. 2):CD003244
9. Raghunath AS, Hungin AP, Mason J, Jackson W. Symptoms in patients on long-term proton pump inhibitors: prevalence and predictors. Aliment Pharmacol Ther 2009;29(4):431-9
10. Fass R, Shapiro M, Dekel R, Sewell J. Systematic review: proton-pump inhibitor failure in gastro-oesophageal reflux disease-where next? Aliment Pharmacol Ther 2005;22(2):79-94 (Pubitemid 41039696)
11. Moore JM, Vaezi MF. Extraesophageal manifestations of gastroesophageal reflux disease: real or imagined? Curr Opin Gastroenterol 2010;26(4):389-94
12. Qadeer MA, Phillips CO, Lopez AR, et al. Proton pump inhibitor therapy for suspected GERD-related chronic laryngitis: a meta-analysis of randomized controlled trials. Am J Gastroenterol 2006;101(11):2646-54 (Pubitemid 44665265)
13. Mackalski BA, Ilnyckyj A. Esophageal pH testing in patients refractory to proton pump inhibitor therapy. Can J Gastroenterol 2008;22(3):249-52 (Pubitemid 351676385)
14. Karamanolis G, Vanuytsel T, Sifrim D, et al. Yield of 24-hour esophageal pH and bilitec monitoring in patients with persisting symptoms on PPI therapy. Dig Dis Sci 2008;53(9):2387-93
15. Orr WC. Reflux events and sleep: are we vulnerable? Curr Gastroenterol Rep 2006;8(3):202-7 (Pubitemid 43862769)
16. Hunt RH. Importance of pH control in the management of GERD. Arch Intern Med 1999;159(7):649-57 (Pubitemid 29177653)
17. Katz PO, Ginsberg GG, Hoyle PE, et al. Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis. Aliment Pharmacol Ther 2007;25(5):617-28
18. Savarino V, Di Mario F, Scarpignato C. Proton pump inhibitors in GORD An overview of their pharmacology, efficacy and safety. Pharmacol Res 2009;59(3):135-53
19. Tack J. Emerging Medical Therapies for the Treatment of GERD. Gastroenterol Hepatol (N Y) 2010;6(9):566-9
20. Asano S, Morii M, Takeguchi N. Molecular and cellular regulation of the gastric proton pump. Biol Pharm Bull 2004;27(1):1-12
21. Hatlebakk JG, Katz PO, Camacho-Lobato L, Castell DO. Proton pump inhibitors: better acid suppression when taken before a meal than without a meal. Aliment Pharmacol Ther 2000;14(10):1267-72
22. Katz PO, Ginsberg GG, Hoyle PE, et al. Relationship between intragastric acid control and healing status in the treatment of moderate to severe erosive oesophagitis. Aliment Pharmacol Ther 2007;25(5):617-28
23. Boeckxstaens GE, Smout A. Systematic review: role of acid, weakly acidic and weakly alkaline reflux in gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2010;32(3):334-43
24. Kahrilas PJ, Howden CW, Hughes N. Response of regurgitation to proton pump inhibitor therapy in clinical trials of gastroesophageal reflux disease. Am J Gastroenterol 2011;106(8):1419-25
25. Dent J. Reflux inhibitor drugs: an emerging novel therapy for gastroesophageal reflux disease. J Dig Dis 2010;11(2):72-5
26. Partosoedarso ER, Abrahams TP, Scullion RT, et al. Cannabinoid1 receptor in the dorsal vagal complex modulates lower oesophageal sphincter relaxation in ferrets. J Physiol 2003;550(Pt 1):149-58 (Pubitemid 36869276)
27. Fass R, Sifrim D. Management of heartburn not responding to proton pump inhibitors. Gut 2009;58(2):295-309
28. Sharma A, Van Oudenhove L, Paine P, et al. Anxiety increases acid-induced esophageal hyperalgesia. Psychosom Med 2010;72(8):802-9
29. Hershcovici T, Achem SR, Jha LK, Fass R. Systematic review: the treatment of noncardiac chest pain. Aliment Pharmacol Ther 2012;35(1):5-14
30. Harnett KM, Rieder F, Behar J, Biancani P. Viewpoints on Acid-induced inflammatory mediators in esophageal mucosa. J Neurogastroenterol Motil 2010;16(4):374-88
31. Caviglia R, Ribolsi M, Maggiano N, et al. Dilated intercellular spaces of esophageal epithelium in nonerosive reflux disease patients with physiological esophageal acid exposure. Am J Gastroenterol 2005;100(3):543-8 (Pubitemid 40487550)
32. Knowles CH, Aziz Q. Visceral hypersensitivity in non-erosive reflux disease. Gut 2008;57(5):674-83 (Pubitemid 351579984)
33. Barlow WJ, Orlando RC. The pathogenesis of heartburn in nonerosive reflux disease: a unifying hypothesis. Gastroenterology 2005;128(3):771-8 (Pubitemid 40585379)
34. Farre R, Fornari F, Blondeau K, et al. Acid and weakly acidic solutions impair mucosal integrity of distal exposed and proximal non-exposed human oesophagus. Gut 2010;59(2):164-9
35. Tobey NA, Hosseini SS, Argote CM, et al. Dilated intercellular spaces and shunt permeability in nonerosive acid-damaged esophageal epithelium. Am J Gastroenterol 2004;99(1):13-22 (Pubitemid 38679095)
36. Farre R, van Malenstein H, De Vos R, et al. Short exposure of oesophageal mucosa to bile acids, both in acidic and weakly acidic conditions, can impair mucosal integrity and provoke dilated intercellular spaces. Gut 2008;57(10):1366-74
37. Farre R, De Vos R, Geboes K, et al. Critical role of stress in increased oesophageal mucosa permeability and dilated intercellular spaces. Gut 2007;56(9):1191-7 (Pubitemid 47300417)
38. Calabrese C, Bortolotti M, Fabbri A, et al. Reversibility of GERD ultrastructural alterations and relief of symptoms after omeprazole treatment. Am J Gastroenterol 2005;100(3):537-42 (Pubitemid 40487549)
39. Caviglia R, Ribolsi M, Gentile M, et al. Dilated intercellular spaces and acid reflux at the distal and proximal oesophagus in patients with non-erosive gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2007;25(5):629-36
40. Tack J. Prokinetics and fundic relaxants in upper functional GI disorders. Curr Opin Pharmacol 2008;8(6):690-6
41. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007;132(1):397-414 (Pubitemid 46127672)
42. Shin JM, Homerin M, Domagala F, et al. Characterization of the inhibitory activity of tenatoprazole on the gastric H+, K+-ATPase in vitro and in vivo. Biochem Pharmacol 2006;71(6):837-49 (Pubitemid 43208840)
43. Galmiche JP, Bruley Des Varannes S, Ducrotte P, et al. Tenatoprazole, a novel proton pump inhibitor with a prolonged plasma half-life: effects on intragastric pH and comparison with esomeprazole in healthy volunteers. Aliment Pharmacol Ther 2004;19(6):655-62 (Pubitemid 38445426)
44. Galmiche JP, Sacher-Huvelin S, Bruley des Varannes S, et al. A comparative study of the early effects of tenatoprazole 40 mg and esomeprazole 40 mg on intragastric pH in healthy volunteers. Aliment Pharmacol Ther 2005;21(5):575-82 (Pubitemid 40381509)
45. Thomson AB, Cohen P, Ficheux H, et al. Comparison of the effects of fasting morning, fasting evening and fed bedtime administration of tenatoprazole on intragastric pH in healthy volunteers: a randomized three-way crossover study. Aliment Pharmacol Ther 2006;23(8):1179-87 (Pubitemid 43779358)
46. Hunt RH, Armstrong D, James C, et al. Effect on intragastric pH of a PPI with a prolonged plasma half-life: comparison between tenatoprazole and esomeprazole on the duration of acid suppression in healthy male volunteers. Am J Gastroenterol 2005;100(9):1949-56
47. Hunt RH, Armstrong D, Yaghoobi M, James C. The pharmacodynamics and pharmacokinetics of S-tenatoprazole-Na 30 mg, 60 mg and 90 mg vs. esomeprazole 40 mg in healthy male subjects. Aliment Pharmacol Ther 2010;31(6):648-57
48. Hershcovici T, Jha LK, Fass R. Dexlansoprazole MR: a review. Ann Med 2011;43(5):366-74
49. Vakily M, Zhang W, Wu J, et al. Pharmacokinetics and pharmacodynamics of a known active PPI with a novel dual delayed release technology, dexlansoprazole MR: a combined analysis of randomized controlled clinical trials. Curr Med Res Opin 2009;25(3):627-38
50. Kukulka M, Eisenberg C, Nudurupati S. Comparator pH study to evaluate the single-dose pharmacodynamics of dual delayed-release dexlansoprazole 60 mg and delayed-release esomeprazole 40 mg. Clin Exp Gastroenterol 2011;4:213-20
51. Sharma P, Shaheen NJ, Perez MC, et al. Clinical trials: healing of erosive oesophagitis with dexlansoprazole MR, a proton pump inhibitor with a novel dual delayed-release formulation-results from two randomized controlled studies. Aliment Pharmacol Ther 2009;29(7):731-41
52. Howden CW, Larsen LM, Perez MC, et al. Clinical trial: efficacy and safety of dexlansoprazole MR 60 and 90 mg in healed erosive oesophagitis- maintenance of healing and symptom relief. Aliment Pharmacol Ther 2009;30(9):895-907
53. Fass R, Chey WD, Zakko SF, et al. Clinical trial: the effects of the proton pump inhibitor dexlansoprazole MR on daytime and nighttime heartburn in patients with non-erosive reflux disease. Aliment Pharmacol Ther 2009;29(12):1261-72
54. Fass R, Inadomi J, Han C, et al. Maintenance of heartburn relief after step-down from twice-daily proton pump inhibitor to once-daily dexlansoprazole modified release. Clin Gastroenterol Hepatol 2011; 10(3):247-53
55. Lee RD, Mulford D, Wu J, Atkinson SN. The effect of time-of-day dosing on the pharmacokinetics and pharmacodynamics of dexlansoprazole MR: evidence for dosing flexibility with a dual delayed release proton pump inhibitor. Aliment Pharmacol Ther 2010;31(9):1001-11
56. Laine L, Katz PO, Johnson DA, et al. Randomised clinical trial: a novel rabeprazole extended release 50 mg formulation vs. esomeprazole 40 mg in healing of moderate-to-severe erosive oesophagitis-the results of two double-blind studies. Aliment Pharmacol Ther 2011;33(2):203-12
57. Morelli G, Chen H, Rossiter G, et al. An open-label, parallel, multiple-dose study comparing the pharmacokinetics and gastric acid suppression of rabeprazole extended-release with esomeprazole 40 mg and rabeprazole delayed-release 20 mg in healthy volunteers. Aliment Pharmacol Ther 2011;33(7):845-54
58. Howden CW. Review article: immediate-release proton-pump inhibitor therapy-potential advantages. Aliment Pharmacol Ther 2005; 22(Suppl 3):25-30 (Pubitemid 41783984)
59. Katz PO, Koch FK, Ballard ED, et al. Comparison of the effects of immediate-release omeprazole oral suspension, delayed-release lansoprazole capsules and delayed-release esomeprazole capsules on nocturnal gastric acidity after bedtime dosing in patients with night-time GERD symptoms. Aliment Pharmacol Ther 2007;25(2):197-205 (Pubitemid 46046376)
60. Castell D, Bagin R, Goldlust B, et al. Comparison of the effects of immediate-release omeprazole powder for oral suspension and pantoprazole delayed-release tablets on nocturnal acid breakthrough in patients with symptomatic gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2005;21(12):1467-74 (Pubitemid 40874164)
61. Howden CW, Ballard ED, Koch FK, et al. Control of 24-hour intragastric acidity with morning dosing of immediate-release and delayed-release proton pump inhibitors in patients with GERD. J Clin Gastroenterol 2009;43(4):323-6
62. Banerjee R, Reddy DN, Guda NM, et al. Oral buffered esomeprazole is superior to i.v. pantoprazole for rapid rise of intragastric pH: a wireless pH-metry analysis. J Gastroenterol Hepatol 2010;25(1):43-7
63. Available from: http://www.vecta.co.il/products-vecam.html
64. Hunt RH, Armstrong D, Yaghoobi M, et al. Predictable prolonged suppression of gastric acidity with a novel proton pump inhibitor, AGN 201904-Z. Aliment Pharmacol Ther 2008;28(2):187-99 (Pubitemid 351861964)
65. Gedda K, Briving C, Svensson K, et al. Mechanism of action of AZD0865, a K+-competitive inhibitor of gastric H+, K+-ATPase. Biochem Pharmacol 2007;73(2):198-205 (Pubitemid 44855722)
66. Kirchhoff P, Andersson K, Socrates T, et al. Characteristics of the K+-competitive H+,K+-ATPase inhibitor AZD0865 in isolated rat gastric glands. Am J Physiol Gastrointest Liver Physiol 2006;291(5):G838-43
67. Nilsson C, Albrektson E, Rydholm H. Tolerability, pharmacokinetics and effects on gastric acid secretion after single oral doses of the potassium-competitive acid blocker AZD0865 in healthy male subjects. Gastroenterology 2005;128(4 Suppl 2):A528
68. Kahrilas PJ, Dent J, Lauritsen K, et al. A randomized, comparative study of three doses of AZD0865 and esomeprazole for healing of reflux esophagitis. Clin Gastroenterol Hepatol 2007;5(12):1385-91 (Pubitemid 350181597)
69. Dent J, Kahrilas PJ, Hatlebakk J, et al. A randomized, comparative trial of a potassium-competitive acid blocker (AZD0865) and esomeprazole for the treatment of patients with nonerosive reflux disease. Am J Gastroenterol 2008;103(1):20-6
70. Shin JM, Inatomi N, Munson K, et al. Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl] -N-methylmethanamine monofumarate (TAK-438). J Pharmacol Exp Ther 2011;339(2):412-20
71. Hori Y, Matsukawa J, Takeuchi T, et al. A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals. J Pharmacol Exp Ther 2011;337(3):797-804
72. Matsukawa J, Hori Y, Nishida H, et al. A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands. Biochem Pharmacol 2011;81(9):1145-51
73. Blackshaw LA, Staunton E, Lehmann A, Dent J. Inhibition of transient LES relaxations and reflux in ferrets by GABA receptor agonists. Am J Physiol 1999;277(4 Pt 1):G867-74 (Pubitemid 29525939)
74. Lehmann A, Antonsson M, Bremner-Danielsen M, et al. Activation of the GABA(B) receptor inhibits transient lower esophageal sphincter relaxations in dogs. Gastroenterology 1999;117(5):1147-54 (Pubitemid 29512674)
75. Lee KJ, Vos R, Janssens J, Tack J. Differential effects of baclofen on lower oesophageal sphincter pressure and proximal gastric motility in humans. Aliment Pharmacol Ther 2003;18(2):199-207 (Pubitemid 36951656)
76. Lidums I, Lehmann A, Checklin H, et al. Control of transient lower esophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in normal subjects. Gastroenterology 2000;118(1):7-13 (Pubitemid 30020367)
77. van Herwaarden MA, Samsom M, Rydholm H, Smout AJ. The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux disease. Aliment Pharmacol Ther 2002;16(9):1655-62
78. Zhang Q, Lehmann A, Rigda R, et al. Control of transient lower oesophageal sphincter relaxations and reflux by the GABA(B) agonist baclofen in patients with gastro-oesophageal reflux disease. Gut 2002;50(1):19-24 (Pubitemid 34028297)
79. Koek GH, Sifrim D, Lerut T, et al. Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors. Gut 2003;52(10):1397-402 (Pubitemid 37176716)
80. Lehmann A. GABAB receptors as drug targets to treat gastroesophageal reflux disease. Pharmacol Ther 2009;122(3):239-45
81. Lehmann A, Antonsson M, Holmberg AA, et al. (R)-(3-amino-2-fluoropropyl) phosphinic acid (AZD3355), a novel GABAB receptor agonist, inhibits transient lower esophageal sphincter relaxation through a peripheral mode of action. J Pharmacol Exp Ther 2009;331(2):504-12
82. Boeckxstaens GE, Rydholm H, Lei A, et al. Effect of lesogaberan, a novel GABA(B)-receptor agonist, on transient lower oesophageal sphincter relaxations in male subjects. Aliment Pharmacol Ther 2010;31(11):1208-17
83. Boeckxstaens GE, Beaumont H, Mertens V, et al. Effects of lesogaberan on reflux and lower esophageal sphincter function in patients with gastroesophageal reflux disease. Gastroenterology 2010;139(2):409-17
84. Boeckxstaens GE, Beaumont H, Hatlebakk JG, et al., et al. A novel reflux inhibitor lesogaberan (AZD3355) as add-on treatment in patients with GORD with persistent reflux symptoms despite proton pump inhibitor therapy: a randomised placebo-controlled trial. Gut 2011;60(9):1182-8
85. Shaheen N, Denison H, Bjorck K, et al. Efficacy of a novel g-aminobutyric acid type B receptor (GABAB) agonist, lesogaberan, as an add-on to proton pump inhibitor (PPI) therapy in the treatment of gastroesophageal reflux disease in patients who have a partial response to PPI therapy. Gastroenterology 2011; 140(Suppl 1):S-580
86. Lal R, Sukbuntherng J, Tai EH, et al. Arbaclofen placarbil, a novel R-baclofen prodrug: improved absorption, distribution, metabolism, and elimination properties compared with R-baclofen. J Pharmacol Exp Ther 2009;330(3):911-21
87. Gerson LB, Huff FJ, Hila A, et al. Arbaclofen placarbil decreases postprandial reflux in patients with gastroesophageal reflux disease. Am J Gastroenterol 2010;105(6):1266-75
88. Vakil NB, Huff FJ, Bian A, et al. Arbaclofen placarbil in GERD: a randomized, double-blind, placebo-controlled study. Am J Gastroenterol 2011;106(8):1427-38
89. Keywood C, Wakefield M, Tack J. A proof-of-concept study evaluating the effect of ADX10059, a metabotropic glutamate receptor-5 negative allosteric modulator, on acid exposure and symptoms in gastro-oesophageal reflux disease. Gut 2009;58(9):1192-9
90. Zerbib F, Keywood C, Strabach G. Efficacy, tolerability and pharmacokinetics of a modified release formulation of ADX10059, a negative allosteric modulator of metabotropic glutamate receptor 5: an esophageal pH-impedance study in healthy subjects. Neurogastroenterol Motil 2010;22(8):859-65, e231
91. Zerbib F, Bruley des Varannes S, Roman S, et al. Randomised clinical trial: effects of monotherapy with ADX10059, a mGluR5 inhibitor, on symptoms and reflux events in patients with gastro-oesophageal reflux disease. Aliment Pharmacol Ther 2011;33(8):911-21
92. Beaumont H, Jensen J, Carlsson A, et al. Effect of delta9- tetrahydrocannabinol, a cannabinoid receptor agonist, on the triggering of transient lower oesophageal sphincter relaxations in dogs and humans. Br J Pharmacol 2009;156(1):153-62
93. Scarpellini E, Blondeau K, Boecxstaens V, et al. Effect of rimonabant on oesophageal motor function in man. Aliment Pharmacol Ther 2011;33(6):730-7
94. Krarup AL, Ny L, Astrand M, et al. Randomised clinical trial: the efficacy of a transient receptor potential vanilloid 1 antagonist AZD1386 in human oesophageal pain. Aliment Pharmacol Ther 2011;33(10):1113-22
95. McCallum RW, Ippoliti AF, Cooney C, Sturdevant RA. A controlled trial of metoclopramide in symptomatic gastroesophageal reflux. N Engl J Med 1977;296(7):354-7 (Pubitemid 8047170)
96. McCallum RW, Fink SM, Winnan GR, et al. Metoclopramide in gastroesophageal reflux disease: rationale for its use and results of a double-blind trial. Am J Gastroenterol 1984;79(3):165-72 (Pubitemid 14157879)
97. McCallum RW, Fink SM, Lerner E, Berkowitz DM. Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 1983;84(6):1573-7 (Pubitemid 13092109)
98. DiPalma JR. Metoclopramide: a dopamine receptor antagonist. Am Fam Physician 1990;41(3):919-24 (Pubitemid 20100263)
99. Quigley EM. Cisapride: what can we learn from the rise and fall of a prokinetic? J Dig Dis 2011;12(3):147-56
100. Champion MC. Prokinetic therapy in gastroesophageal reflux disease. Can J Gastroenterol 1997;11(Suppl B):55B-65B
101. Arai K, Takeuchi Y, Watanabe H, et al. Prokinetics influence the pharmacokinetics of rabeprazole. Digestion 2008;78(2-3):67-71
102. Kamiya T, Adachi H, Hirako M, et al. Impaired gastric motility and its relationship to reflux symptoms in patients with nonerosive gastroesophageal reflux disease. J Gastroenterol 2009;44(3):183-9
103. Futagami S, Iwakiri K, Shindo T, et al. The prokinetic effect of mosapride citrate combined with omeprazole therapy improves clinical symptoms and gastric emptying in PPI-resistant NERD patients with delayed gastric emptying. J Gastroenterol 2010;45(4):413-21
104. Madan K, Ahuja V, Kashyap PC, Sharma MP. Comparison of efficacy of pantoprazole alone versus pantoprazole plus mosapride in therapy of gastroesophageal reflux disease: a randomized trial. Dis Esophagus 2004;17(4):274-8 (Pubitemid 40123800)
105. Miwa H, Inoue K, Ashida K, et al. Randomised clinical trial: efficacy of the addition of a prokinetic, mosapride citrate, to omeprazole in the treatment of patients with non-erosive reflux disease-a double-blind, placebocontrolled study. Aliment Pharmacol Ther 2011;33(3):323-32
106. Kido T, Nakai Y, Kase Y, et al. Effects of rikkunshi-to, a traditional Japanese medicine, on the delay of gastric emptying induced by N(G)-nitro-L-arginine. J Pharmacol Sci 2005;98(2):161-7 (Pubitemid 40943722)
107. Tominaga K, Kido T, Ochi M, et al. The traditional Japanese medicine rikkunshito promotes gastric emptying via the antagonistic action of the 5-HT3 receptor pathway in rats. Evid Based Complement Alternat Med 2011;2011:248481, 1-8
108. Kawahara H, Kubota A, Hasegawa T, et al. Effects of rikkunshito on the clinical symptoms and esophageal acid exposure in children with symptomatic gastroesophageal reflux. Pediatr Surg Int 2007;23(10):1001-5 (Pubitemid 47437358)
109. Tominaga K, Iwakiri R, Fujimoto K, et al. Rikkunshito improves symptoms in PPI-refractory GERD patients: a prospective, randomized, multicenter trial in Japan. J Gastroenterol 2012;47(3):284-92
110. Kim YS, Kim TH, Choi CS, et al. Effect of itopride, a new prokinetic, in patients with mild GERD: a pilot study. World J Gastroenterol 2005;11(27):4210-14 (Pubitemid 41086873)
111. Scarpellini E, Vos R, Blondeau K, et al. The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man. Aliment Pharmacol Ther 2011;33(1):99-105
112. Ezzat WF, Fawaz SA, Fathey H, El Demerdash A. Virtue of adding prokinetics to proton pump inhibitors in the treatment of laryngopharyngeal reflux disease: prospective study. J Otolaryngol Head Neck Surg 2011;40(4):350-6
113. Talley NJ, Tack J, Ptak T, et al. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials. Gut 2008;57(6):740-6 (Pubitemid 351716964)