Pharmacologic, pharmacokinetic, and pharmacogenomic aspects of functional gastrointestinal disorders

Gastroenterology

Volumn 150, Issue 6, 2016, Pages 1319-1331.e20

  Camilleri, Michael ^a   Buéno, Lionel ^b   Andresen, Viola ^c   De Ponti, Fabrizio ^d   Choi, Myung Gyu ^e   Lembo, Anthony ^f  

^a Mayo Clinic College of Medicine   (United States)

^b CEMAGREF   (France)

^c UNIVERSITY OF HAMBURG   (Germany)

^d UNIVERSITY OF BOLOGNA   (Italy)

^e The Catholic University of Korea College of Medicine   (South Korea)

^f BETH ISRAEL DEACONESS MEDICAL CENTER   (United States)

Author keywords

Animal Models; Constipation; Diarrhea; Dyspepsia; Pain; Sensation; Transit

Indexed keywords

17 METHYLNALTREXONE; BIOLOGICAL MARKER; CAMICINAL; CAPSAICIN; CHOLINESTERASE INHIBITOR; DEXLOXIGLUMIDE; DOLCANATIDE; DOPAMINE RECEPTOR BLOCKING AGENT; ELOBIXIBAT; GASTROINTESTINAL AGENT; LINACLOTIDE; LOXIGLUMIDE; LUBIPROSTONE; MOSAPRIDE; MOTILIDE; MU OPIATE RECEPTOR AGONIST; NALOXEGOL; NARONAPRIDE; NEW DRUG; PLECANATIDE; PRUCALOPRIDE; RELAMORELIN; RELENOPRIDE; RM 131; SEROTONIN AGONIST; TENAPANOR; TETRAHYDROCANNABINOL; ULIMORELIN; UNCLASSIFIED DRUG; UNINDEXED DRUG; VELUSETRAG;

ABDOMINAL PAIN; ALLODYNIA; ARTICLE; CHRONIC CONSTIPATION; CHRONIC DIARRHEA; COLON MOTILITY; CONSTIPATION; DIGESTIVE SYSTEM FUNCTION DISORDER; DRUG DEVELOPMENT; DRUG EFFECT; DRUG HALF LIFE; DRUG INDUCED DISEASE; DRUG METABOLISM; DYSPEPSIA; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRANSIT; GENETIC POLYMORPHISM; HUMAN; HYPERALGESIA; IRRITABLE COLON; MECHANICAL STIMULATION; NONHUMAN; OPIOID INDUCED CONSTIPATION; PERCEPTIVE THRESHOLD; PERSONALIZED MEDICINE; PHARMACOGENETICS; PHARMACOGENOMICS; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRECLINICAL STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RECTUM MOTILITY; STOMACH EMPTYING; STOMACH PARESIS; VISCERAL PAIN;

EID: 84964792423     PISSN: 00165085     EISSN: 15280012     Source Type: Journal    
DOI: 10.1053/j.gastro.2016.02.029     Document Type: Article

References (269)

1. M.L. Rouzade, J. Fioramonti, and L. Buéno A model for evaluation of gastric sensitivity in awake rats Neurogastroenterol Motil 10 1998 157 163
2. T. Mori, K. Kawano, and T. Shishikura 5-HT3-receptor antagonist inhibits visceral pain differently in chemical and mechanical stimuli in rats J Pharmacol Sci 94 2004 73 76
3. D. Louvel, M. Delvaux, G. Staumont, and et al. Intracolonic injection of glycerol: a model for abdominal pain in irritable bowel syndrome? Gastroenterology 110 1996 351 361
4. M. Bouin, M. Delvaux, C. Blanc, and et al. Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance Eur J Gastroenterol Hepatol 13 2001 573 580
5. O. Morteau, T. Hachet, M. Caussette, and et al. Experimental colitis alters visceromotor response to colorectal distension in awake rats Dig Dis Sci 39 1994 1239 1248
6. E.D. Al Chaer, M. Kawasaki, and P.J. Pasricha A new model of chronic visceral hypersensitivity in adult rats induced by colon irritation during postnatal development Gastroenterology 119 2000 1276 1285
7. M. Gue, C. Rio-Lacheze, H. Eutamene, and et al. Stress-induced visceral hypersensitivity to rectal distension in rats: role of CRF and mast cells Neurogastroenterol Motil 9 1997 271 279
8. A.M. Coelho, J. Fioramonti, and L. Bueno Systemic lipopolysaccharide influences rectal sensitivity in rats: role of mast cells, cytokines, and vagus nerve Am J Physiol 279 2000 G781 G790
9. F. Barreau, C. Cartier, L. Ferrier, and et al. Nerve growth factor mediates alterations of colonic sensitivity and mucosal barrier induced by neonatal stress in rats Gastroenterology 127 2004 524 534
10. R.S. Woodsworth, and C.S. Sherrington A pseudo affective reflex and its spinal path J Physiol 31 1904 234 243
11. E.H. Kamp, R.C. Jones III, S.R. Tillman, and et al. Quantitative assessment and characterization of visceral nociception and hyperalgesia in mice Am J Physiol 284 2003 G434 G444
12. N. Ozaki, K. Bielefeldt, J.N. Sengupta, and et al. Models of gastric hyperalgesia in the rat Am J Physiol 283 2002 G666 G676
13. T.J. Ness, and G.F. Gebhart Colorectal distension as a noxious visceral stimulus: physiologic and pharmacologic characterization of pseudo affective reflexes in the rat Brain Res 450 1988 153 169
14. X. Su, V. Julia, and G.F. Gebhart Effects of intracolonic opioid receptor agonists on polymodal pelvic nerve afferent fibers in the rat J Neurophysiol 83 2000 963 970
15. C.E. Booth, A.J. Kirkup, G.A. Hicks, and et al. Somatostatin sst(2) receptor-mediated inhibition of mesenteric afferent nerves of the jejunum in the anesthetized rat Gastroenterology 121 2001 358 369
16. J. Fioramonti, E. Gaultier, M. Toulouse, and et al. Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action Neurogastroenterol Motil 15 2003 363 369
17. A.C. Johnson, B. Myers, J. Lazovic, and et al. Brain activation in response to visceral stimulation in rats with amygdala implants of corticosterone: an FMRI study PLoS One 5 2010 e8573
18. P.G. McLean, C. Picard, R. Garcia-Villar, and et al. Effects of nematode infection on sensitivity to intestinal distension: role of tachykinin NK2 receptors Eur J Pharmacol 337 1997 279 282
19. M. Gue, J.L. Junien, and L. Buéno The kappa agonist fedotozine modulates colonic distention-induced inhibition of gastric motility and emptying in dogs Gastroenterology 107 1994 1327 1334
20. H.C. Tjeerdsma, A.J. Smout, and L.M. Akkermans Voluntary suppression of defecation delays gastric emptying Dig Dis Sci 38 1993 832 836
21. K.J. Lee, and J. Tack Duodenal implications in the pathophysiology of functional dyspepsia J Neurogastroenterol Motil 16 2010 251 257
22. M. Gue, T. Peeters, I. Depoortere, and et al. Stress-induced changes in gastric emptying, postprandial motility, and plasma gut hormone levels in dogs Gastroenterology 97 1989 1101 1107
23. A.A. Al-Qarawi, B.H. Ali, S.A. Al-Mougy, and et al. Gastrointestinal transit in mice treated with various extracts of date (Phoenix dactylifera L.) Food Chem Toxicol 41 2003 37 39
24. M. Broccardo, G. Improta, and A. Tabacco Central effect of SNC 80, a selective and systemically active delta-opioid receptor agonist, on gastrointestinal propulsion in the mouse Eur J Pharmacol 342 1998 247 251
25. C.L. Williams, J.M. Peterson, R.G. Villar, and et al. Corticotropin-releasing factor directly mediates colonic responses to stress Am J Physiol 253 1987 G582 G586
26. M. Kadowaki, P.R. Wade, and M.D. Gershon Participation of 5-HT3, 5-HT4, and nicotinic receptors in the peristaltic reflex of guinea pig distal colon Am J Physiol 271 1996 G849 G857
27. P.A. Cann, N.W. Read, and C.O. Holdsworth What is the benefit of coarse wheat bran in patients with irritable bowel syndrome? Gut 25 1984 168 173
28. P.A. Cann, N.W. Read, C.D. Holdsworth, and et al. Role of loperamide and placebo in management of irritable bowel syndrome Dig Dis Sci 29 1984 239 247
29. F. Cremonini, S. Delgado-Aros, and M. Camilleri Efficacy of alosetron in irritable bowel syndrome: a meta-analysis of randomized controlled trials Neurogastroenterol Motil 15 2003 79 86
30. S.A. Muller-Lissner, I. Fumagalli, K.D. Bardhan, and et al. Tegaserod, a 5-HT4 receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation Aliment Pharmacol Ther 15 2001 1655 1666
31. J. Novick, P. Miner, R. Krause, and et al. A randomized, double-blind, placebo-controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation Aliment Pharmacol Ther 16 2002 1877 1888
32. J. Kellow, O.Y. Lee, F.Y. Chang, and et al. An Asia-Pacific, double blind, placebo controlled, randomised study to evaluate the efficacy, safety, and tolerability of tegaserod in patients with irritable bowel syndrome Gut 52 2003 671 676
33. A.V. Emmanuel, A.J. Roy, T.J. Nicholls, and et al. Prucalopride, a systemic enterokinetic, for the treatment of constipation Aliment Pharmacol Ther 16 2002 1347 1356
34. E.P. Bouras, M. Camilleri, D.D. Burton, and et al. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder Gastroenterology 120 2001 354 360
35. V. Andresen, M. Camilleri, I.A. Busciglio, and et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome Gastroenterology 133 2007 761 768
36. W.D. Chey, A.J. Lembo, B.J. Lavins, and et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety Am J Gastroenterol 107 2012 1702 1712
37. S. Rao, A.J. Lembo, S.J. Shiff, and et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation Am J Gastroenterol 107 2012 1714 1724
38. M.R. von der Ohe, M. Camilleri, L.K. Kvols, and et al. Motor dysfunction of the small bowel and colon in patients with the carcinoid syndrome and diarrhea N Engl J Med 329 1993 1073 1078
39. V. Plourde, T. Lembo, Z. Shui, and et al. Effects of the somatostatin analogue octreotide on rectal afferent nerves in human Am J Physiol 265 1993 G751
40. W.L. Hasler, H.C. Soudah, and C. Owyang A somatostatin analogue inhibits afferent pathways mediating perception of rectal distention Gastroenterology 104 1993 1390 1397
41. W. Hasler, H.C. Soudah, and C. Owyang Somatostatin analog inhibits afferent response to rectal distention in diarrhea-predominant irritable bowel patients J Pharmacol Exp Ther 268 1994 1206 1211
42. M. Bradette, M. Delvaux, G. Staumont, and et al. Octreotide increases thresholds of colonic visceral perception in IBS patients without modifying muscle tone Dig Dis Sci 39 1994 1171 1178
43. T. Lembo, B.D. Naliboff, K. Matin, and et al. Irritable bowel syndrome patients show altered sensitivity to exogenous opioids Pain 87 2000 137 147
44. B. Coffin, J.P. Farmachidi, P. Rueegg, and et al. Tegaserod, a 5-HT4 receptor partial agonist, decreases sensitivity to rectal distension in healthy subjects Aliment Pharmacol Ther 17 2003 577 585
45. A. Sturm, G. Holtmann, H. Goebell, and et al. Prokinetics in patients with gastroparesis: a systematic analysis Digestion 60 1999 422 427
46. K. Maganti, K. Onyemere, and M.P. Jones Oral erythromycin and symptomatic relief of gastroparesis: a systematic review Am J Gastroenterol 98 2003 259 263
47. P. Janssen, M.S. Harris, M. Jones, and et al. The relation between symptom improvement and gastric emptying in the treatment of diabetic and idiopathic gastroparesis Am J Gastroenterol 108 2013 1382 1391
48. M.A. Verhagen, M. Samsom, B. Maes, and et al. Effects of a new motilide, ABT-229, on gastric emptying and postprandial antroduodenal motility in healthy volunteers Aliment Pharmacol Ther 11 1997 1077 1086
49. N.J. Talley, M. Verlinden, W. Snape, and et al. Failure of a motilin receptor agonist (ABT-229) to relieve the symptoms of functional dyspepsia in patients with and without delayed gastric emptying: a randomized double-blind placebo-controlled trial Aliment Pharmacol Ther 14 2000 1653 1661
50. N.J. Talley, M. Verlinden, D.J. Geenen, and et al. Effects of a motilin receptor agonist (ABT-229) on upper gastrointestinal symptoms in type 1 diabetes mellitus: a randomized, double-blind, placebo-controlled trial Gut 49 2001 395 401
51. F. Cremonini, B.P. Mullan, M. Camilleri, and et al. Performance characteristics of scintigraphic transit measurements for studies of experimental therapies Aliment Pharmacol Ther 16 2002 1781 1790
52. J. Tack, B. Van Elzen, G. Tytgat, and et al. A placebo-controlled trial of the 5-HT1A agonist R-137696 on symptoms, visceral hypersensitivity and on impaired accommodation in functional dyspepsia Gastroenterology 126 Suppl 2 2004 A70
53. N.W. Read, J.L. Abitbol, K.D. Bardhan, and et al. Efficacy and safety of the peripheral kappa agonist fedotozine versus placebo in the treatment of functional dyspepsia Gut 41 1997 664 668
54. H.J. Chial, C. Camilleri, S. Delgado-Aros, and et al. A nutrient drink test to assess maximum tolerated volume and postprandial symptoms: effects of gender, body mass index and age in health Neurogastroenterol Motil 14 2002 249 253
55. J. Arts, P. Caenepeel, K. Verbeke, and et al. Influence of erythromycin on gastric emptying and meal related symptoms in functional dyspepsia with delayed gastric emptying Gut 54 2005 455 460
56. B. Braak, T.K. Klooker, M.M. Wouters, and et al. Randomised clinical trial: the effects of amitriptyline on drinking capacity and symptoms in patients with functional dyspepsia, a double-blind placebo-controlled study Aliment Pharmacol Ther 34 2011 638 648
57. P. Janssen, S. Verschueren, H.G. Ly, and et al. Intragastric pressure during food intake: a physiological and minimally invasive method to assess gastric accommodation Neurogastroenterol Motil 23 2011 316 322 e153
58. H.P. Simonian, A.H. Maurer, L.C. Knight, and et al. Simultaneous assessment of gastric accommodation and emptying: studies with liquid and solid meals J Nucl Med 45 2004 1155 1160
59. E.P. Bouras, S. Delgado-Aros, M. Camilleri, and et al. SPECT imaging of the stomach: comparison with barostat, and effects of sex, age, body mass index, and fundoplication. Single photon emission computed tomography Gut 51 2002 781 786
60. J. Sistonen, S. Fuselli, J.U. Palo, and et al. Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales Pharmacogenet Genomics 19 2009 170 179
61. W.M. Gonsalkorale, C. Perrey, V. Pravica, and et al. Interleukin 10 genotypes in irritable bowel syndrome: evidence for an inflammatory component? Gut 52 2003 91 93
62. M. Camilleri Is there a SERT-ain association with IBS? Gut 53 2004 1396 1399
63. G. Holtmann, W. Siffert, S. Haag, and et al. G-protein beta 3 subunit 825 CC genotype is associated with unexplained (functional) dyspepsia Gastroenterology 126 2004 971 979
64. P. Dalen, M.L. Dahl, M.L. Ruiz, and et al. 10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes Clin Pharmacol Ther 63 1998 444 452
65. C.E. Glatt, and V.I. Reus Pharmacogenetics of monoamine transporters Pharmacogenomics 4 2003 583 596
66. M. Camilleri, E. Atanasova, P.J. Carlson, and et al. Serotonin-transporter polymorphism pharmacogenetics in diarrhea-predominant irritable bowel syndrome Gastroenterology 123 2002 425 432
67. Y. Li, Y. Nie, J. Xie, and et al. The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and its influence on tegaserod treatment in Chinese patients Dig Dig Sci 52 2007 2942 2949
68. A. Lembo, and M. Camilleri Chronic constipation N Engl J Med 349 2003 1360 1368
69. L. O'Mahony, J. McCarthy, P. Kelly, and et al. A randomized, placebo-controlled, double-blind comparison of the probiotic bacteria lactobacillus and bifidobacterium in irritable bowel syndrome (IBS): symptom responses and relationship to cytokine profiles Gastroenterology 128 2005 541 551
70. D. Lesbros-Pantoflickova, P. Michetti, M. Fried, and et al. Meta-analysis: the treatment of irritable bowel syndrome Aliment Pharmacol Ther 20 2004 1253 1269
71. M.D. Gershon, and G.M. Jonakait Uptake and release of 5-hydroxytryptamine by enteric 5-hydroxytryptaminergic neurones: effects of fluoxetine (Lilly 110140) and chlorimipramine Br J Pharmacol 66 1979 7 9
72. D.A. Gorard, G.W. Libby, and M.J. Farthing 5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake Gut 35 1994 496 500
73. F. De Ponti Pharmacology of serotonin: what a clinician should know Gut 53 2004 1520 1535
74. E.P. Bouras, M. Camilleri, D.D. Burton, and et al. Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans Gut 44 1999 682 686
75. A.C. Poen, R.J. Felt-Bersma, P.A. Van Dongen, and et al. Effect of prucalopride, a new enterokinetic agent, on gastrointestinal transit and anorectal function in healthy volunteers Aliment Pharmacol Ther 13 1999 1493 1497
76. L. Degen, D. Matzinger, M. Merz, and et al. Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects Aliment Pharmacol Ther 15 2001 1745 1751
77. H.C. Lim, J.H. Kim, Y.H. Youn, and et al. Effects of the addition of mosapride to gastroesophageal reflux disease patients on proton pump inhibitor: a prospective randomized, double-blind study J Neurogastroenterol Motil 19 2013 495 502
78. K. Fukazawa, K. Furuta, K. Adachi, and et al. Effects of mosapride on esophageal motor activity and esophagogastric junction compliance in healthy volunteers J Gastroenterol 49 2014 1307 1313
79. Y.K. Cho, M.G. Choi, E.Y. Park, and et al. Effect of mosapride combined with esomeprazole improves esophageal peristaltic function in patients with gastroesophageal reflux disease: a study using high resolution manometry Dig Dis Sci 58 2013 1035 1041
80. M. Hongo, S. Harasawa, T. Mine, and et al. Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study (JMMS) J Gastroenterol Hepatol 27 2012 62 68
81. J. Tack, R. Vos, J. Janssens, and et al. Influence of tegaserod on proximal gastric tone and on the perception of gastric distension Aliment Pharmacol Ther 18 2003 1031 1037
82. M. Tonini, L. Cipollina, E. Poluzzi, and et al. Review article: clinical implications of enteric and central D2 receptor blockade by antidopaminergic gastrointestinal prokinetics Aliment Pharmacol Ther 19 2004 379 390
83. P. Moayyedi, S. Soo, J. Deeks, and et al. Pharmacological interventions for non-ulcer dyspepsia Cochrane Database Syst Rev 2004 CD001960
84. S.J. Veldhuyzen van Zanten, M.J. Jones, M. Verlinden, and et al. Efficacy of cisapride and domperidone in functional (nonulcer) dyspepsia: a meta-analysis Am J Gastroenterol 96 2001 689 696
85. H.P. Parkman, M.R. Carlson, and D. Gonyer Metoclopramide nasal spray is effective in symptoms of gastroparesis in diabetics compared to conventional oral tablet Neurogastroenterol Motil 26 2014 521 528
86. M. Rossi, and G. Giorgi Domperidone and long QT syndrome Curr Drug Saf 5 2010 257 262
87. European Medicines Agency's Pharmacovigilance Risk Assessment Committee (PRAC) recommends restricting use of domperidone. (http://www.ema.europa.eu/docs/en-GB/document-library/Referrals-document/Domperidone-31/Recommendation-provided-by-Pharmacovigilance-Risk-Assessment-Committee/WC500162559.pdf. Accessed February 23, 2015.
88. X. Huang, B. Lv, S. Zhang, and et al. Itopride therapy for functional dyspepsia: a meta-analysis World J Gastroenterol 18 2012 7371 7377
89. N.J. Talley, J. Tack, T. Ptak, and et al. Itopride in functional dyspepsia: results of two phase III multicentre, randomised, double-blind, placebo-controlled trials Gut 57 2008 740 746
90. G. Holtmann, N.J. Talley, T. Liebregts, and et al. A placebo-controlled trial of itopride in functional dyspepsia N Engl J Med 354 2006 832 840
91. Z. Itoh Motilin and clinical application Peptides 18 1997 593 608
92. R. Cuomo, P. Vandaele, B. Coulie, and et al. Influence of motilin on gastric fundus tone and on meal-induced satiety in man: role of cholinergic pathways Am J Gastroenterol 101 2006 804 811
93. Bruley d, V, V. Parys, A. Ropert, and et al. Erythromycin enhances fasting and postprandial proximal gastric tone in humans Gastroenterology 109 1995 32 39
94. H. Piessevaux, J. Tack, A. Wilmer, and et al. Perception of changes in wall tension of the proximal stomach in humans Gut 49 2001 203 208
95. V. Annese, J. Janssens, G. Vantrappen, and et al. Erythromycin accelerates gastric emptying by inducing antral contractions and improved gastroduodenal coordination Gastroenterology 102 1992 823 828
96. S.D. Bologna, W.L. Hasler, and C. Owyang Down-regulation of motilin receptors on rabbit colon myocytes by chronic oral erythromycin J Pharmacol Exp Ther 266 1993 852 856
97. J. Broad, S. Mukherjee, M. Samadi, and et al. Regional- and agonist-dependent facilitation of human neurogastrointestinal functions by motilin receptor agonists Br J Pharmacol 167 2012 763 774
98. G.J. Sanger, S.M. Westaway, A.A. Barnes, and et al. GSK962040: a small molecule, selective motilin receptor agonist, effective as a stimulant of human and rabbit gastrointestinal motility Neurogastroenterol Motil 21 2009 657 664 e30-e31
99. S. Leming, J. Broad, S.J. Cozens, and et al. GSK962040: a small molecule motilin receptor agonist which increases gastrointestinal motility in conscious dogs Neurogastroenterol Motil 23 2011 958-e410
100. K. Matsueda, M. Hongo, J. Tack, and et al. A placebo-controlled trial of acotiamide for meal-related symptoms of functional dyspepsia Gut 61 2012 821 828
101. K. Matsueda, M. Hongo, J. Tack, and et al. 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 22 2010 618-e173
102. J. Tack, A. Masclee, R. Heading, and et al. A dose-ranging, placebo-controlled, pilot trial of Acotiamide in patients with functional dyspepsia Neurogastroenterol Motil 21 2009 272 280
103. N. Ejskjaer, E.T. Vestergaard, P.M. Hellström, and et al. Ghrelin receptor agonist (TZP-101) accelerates gastric emptying in adults with diabetes and symptomatic gastroparesis Aliment Pharmacol Ther 29 2009 1179 1187
104. N. Ejskjaer, G. Dimcevski, J. Wo, and 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 22 2010 1069-e281
105. J.M. Wo, N. Ejskjaer, P.M. Hellström, and et al. Randomised clinical trial: ghrelin agonist TZP-101 relieves gastroparesis associated with severe nausea and vomiting - randomized clinical study subset data Aliment Pharmacol Ther 33 2011 679 688
106. D. Ang, H. Nicolai, R. Vos, and et al. Influence of ghrelin on the gastric accommodation reflex and on meal-induced satiety in man Neurogastroenterol Motil 21 2009 528 533
107. N. Ejskjaer, J.M. Wo, T. Esfandyari, and et al. A phase 2a, randomized, double-blind 28-day study of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis Neurogastroenterol Motil 25 2013 e140 e150
108. R.W. McCallum, A. Lembo, T. Esfandyari, et al. TZP-102 Phase 2b Study Group Phase 2b, randomized, double-blind 12-week studies of TZP-102, a ghrelin receptor agonist for diabetic gastroparesis Neurogastroenterol Motil 25 2013 e705 e717
109. A. Shin, M. Camilleri, I. Busciglio, and et al. Randomized, placebo-controlled, single-dose, crossover study of the effects of RM-131 in type 2 diabetics with documented delayed gastric emptying Gastroenterology 142 2012 S839
110. A. Lembo, M. Camilleri, R.W. McCallum, and et al. A phase 2, randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of RM-131 in patients with diabetic gastroparesis Gastroenterology 146 Suppl 2014 S158 S159
111. G.E. Dukes, M. Barton, O. Dewit, and et al. Safety/tolerability, pharmacokinetics (PK), and effect on gastric emptying (GE) with 14-days repeat oral dosing of the motilin receptor agonist, GSK962040, in healthy male and female volunteers Neurogastroenterol Motil 22 2010 14 15
112. K. Barshop, and B. Kuo The investigational drug camicinal for the treatment of gastroparesis Expert Opin Investig Drugs 24 2014 1 8
113. J.H. Walsh Gastrointestinal hormones Physiology of the Gastrointestinal Tract 1994 Raven New York 1 128
114. F. De Ponti, and J.R. Malagelada Functional gut disorders: from motility to sensitivity disorders. A review of current and investigational drugs for their management Pharmacol Ther 80 1998 49 88
115. C. Scarpignato, and I. Pelosini Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility Can J Gastroenterol 13 Suppl A 1999 50A 65A
116. C.L. Chan, P. Facer, J.B. Davis, and et al. Sensory fibres expressing capsaicin receptor TRPV1 in patients with rectal hypersensitivity and faecal urgency Lancet 361 2003 385 391
117. M. Bortolotti, G. Coccia, G. Grossi, and et al. The treatment of functional dyspepsia with red pepper Aliment Pharmacol Ther 16 2002 1075 1082
118. S. Frytak, C.G. Moertel, J.R. O'Fallon, and et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo Ann Intern Med 91 1979 825 830
119. R.W. McCallum, I. Soykan, K.R. Sridhar, and et al. Delta-9-tetrahydrocannabinol delays the gastric emptying of solid food in humans: a double-blind, randomized study Aliment Pharmacol Ther 13 1999 77 80
120. R.W. Chapman, V. Stanghellini, M. Geraint, and et al. Randomized clinical trial: macrogol/PEG 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome Am J Gastroenterol 108 2013 1508 1515
121. A.M. Connell The motility of the pelvic colon. II. Paradoxical motility in diarrhoea and constipation Gut 3 1962 342 348
122. P.G. Dinning, L. Wiklendt, L. Maslen, and et al. Colonic motor abnormalities in slow transit constipation defined by high resolution, fiber-optic manometry Neurogastroenterol Motil 27 2015 379 388
123. D.Y. Kim, and M. Camilleri Serotonin: a mediator of the brain-gut connection Am J Gastroenterol 95 2000 2698 2709
124. J.M. Hoffman, K. Tyler, S.J. MacEachern, and et al. Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity Gastroenterology 142 2012 844 854
125. J.H. Demaever, R.A. Lefebvre, and J.A.J. Schuurkes 5-HT4 receptor agonists: similar but not the same Neurogastroenterol Motil 20 2008 99 112
126. M. Camilleri, R. Kerstens, A. Rykx, and et al. A placebo-controlled trial of prucalopride for severe chronic constipation N Engl J Med 358 2008 2344 2354
127. M. Ke, D. Zou, Y. Yuan, and 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 24 2012 999-e541
128. B. Mendzelevski, J. Ausma, D.O. Chanter, and 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 73 2012 203 209
129. M. Camilleri, M.J. Van Outryve, G. Beyens, and et al. Clinical trial: the efficacy of open-label prucalopride treatment in patients with chronic constipation - follow-up of patients from the pivotal studies Aliment Pharmacol Ther 32 2010 1113 1123
130. M. Camilleri, G. Beyens, R. Kerstens, and et al. Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study Neurogastroenterol Motil 21 2009 1256-e117
131. E.M. Quigley, L. Vandeplassche, R. Kerstens, and et al. 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 29 2009 315 328
132. G. Coremans, R. Kerstens, M. De Pauw, and et al. Prucalopride is effective in patients with severe chronic constipation in whom laxatives fail to provide adequate relief. Results of a double-blind, placebo-controlled clinical trial Digestion 67 2003 82 89
133. S. Müller-Lissner, A. Rykx, R. Kerstens, and et al. A double-blind, placebo-controlled study of prucalopride in elderly patients with chronic constipation Neurogastroenterol Motil 22 2010 991 998 e255
134. M. Goldberg, Y.P. Li, J.F. Johanson, and 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 32 2010 1102 1112
135. M.L. Manini, M. Camilleri, M. Goldberg, and et al. Effects of velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation Neurogastroenterol Motil 22 2010 42 49 e7-e8
136. M. Camilleri, M.I. Vazquez-Roque, D. Burton, and et al. Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans Neurogastroenterol Motil 19 2007 30 38
137. A. Shin, A. Acosta, M. Camilleri, and et al. A randomized trial of 5-hydroxytryptamine 4-receptor agonist, YKP10811, on colonic transit and bowel function in functional constipation Clin Gastroenterol Hepatol 13 2015 701 708 e1
138. M. Gilet, H. Eutamene, H. Han, and et al. Influence of a new 5-HT4 receptor partial agonist, YKP10811, on visceral hypersensitivity in rats triggered by stress and inflammation Neurogastroenterol Motil 26 2014 1761 1770
139. K.E. Barrett, and S.J. Keely Chloride secretion by the intestinal epithelium: molecular basis and regulatory aspects Annu Rev Physiol 62 2000 535 572
140. M. Camilleri Pharmacology of the new treatments for lower gastrointestinal motility disorders and irritable bowel syndrome Clin Pharmacol Ther 91 2012 44 59
141. E. Anggård The biological activities of three metabolites of prostaglandin E 1 Acta Physiol Scand 66 1966 509 510
142. J. Cuppoletti, D.H. Malinowska, J. Chakrabarti, and et al. Effects of lubiprostone on human uterine smooth muscle cells Prostaglandins Other Lipid Mediat 86 2008 56 60
143. E. Raschi, and F. De Ponti Lubiprostone: pharmacokinetic, pharmacodynamic, safety and regulatory aspects in the treatment of constipation-predominant irritable bowel syndrome Expert Opin Drug Metab Toxicol 10 2014 293 305
144. J. Cuppoletti, J. Chakrabarti, K.P. Tewari, and D.H. Malinowska Differentiation between human ClC-2 and CFTR Cl- Am J Physiol Cell Physiol 307 2014 C479 C492
145. D.A. Drossman, W.D. Chey, J.F. Johanson, and et al. Clinical trial: lubiprostone in patients with constipation-associated irritable bowel syndrome - results of two randomized, placebo-controlled studies Aliment Pharmacol Ther 29 2009 329 341
146. J.F. Johanson, and R. Ueno Lubiprostone, a locally acting chloride channel activator, in adult patients with chronic constipation: a double-blind, placebo-controlled, dose-ranging study to evaluate efficacy and safety Aliment Pharmacol Ther 25 2007 1351 1361
147. J.F. Johanson, D. Morton, J. Geenen, and et al. Multicenter, 4-week, double-blind, randomized, placebo-controlled trial of lubiprostone, a locally-acting type-2 chloride channel activator, in patients with chronic constipation Am J Gastroenterol 103 2008 170 177
148. J.F. Johanson, D.A. Drossman, R. Panas, and et al. Clinical trial: phase 2 study of lubiprostone for irritable bowel syndrome with constipation Aliment Pharmacol Ther 27 2008 685 696
149. S. Fukudo, M. Hongo, H. Kaneko, and et al. Efficacy and safety of oral lubiprostone in constipated patients with or without irritable bowel syndrome: a randomized, placebo-controlled and dose-finding study Neurogastroenterol Motil 23 2011 544-e205
150. W.D. Chey, D.A. Drossman, J.F. Johanson, and et al. Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation Aliment Pharmacol Ther 35 2012 587 599
151. N.S. Joo, R.M. London, H.D. Kim, and et al. Regulation of intestinal Cl- and HCO3-secretion by uroguanylin Am J Physiol 274 1998 G633 G644
152. M. Donowitz, B. Cha, N.C. Zachos, and et al. NHERF family and NHE3 regulation J Physiol 567 2005 3 11
153. J. Castro, A.M. Harrington, P.A. Hughes, and et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3',5'-monophosphate Gastroenterology 145 2013 1334 1346 e1-e11
154. A.J. Lembo, H.A. Schneier, S.J. Shiff, and et al. Two randomized trials of linaclotide for chronic constipation N Engl J Med 365 2011 527 536
155. A.J. Lembo, C.B. Kurtz, J.E. Macdougall, and et al. Efficacy of linaclotide for patients with chronic constipation Gastroenterology 138 2010 886 895
156. E.M. Quigley, J. Tack, W.D. Chey, and et al. Randomised clinical trials: linaclotide phase 3 studies in IBS-C - a prespecified further analysis based on European Medicines Agency-specified endpoints Aliment Pharmacol Ther 37 2013 49 61
157. S. Rao, A.J. Lembo, S.J. Shiff, and et al. A 12-week, randomized, controlled trial with a 4-week randomized withdrawal period to evaluate the efficacy and safety of linaclotide in irritable bowel syndrome with constipation Am J Gastroenterol 107 2012 1714 1724
158. W.D. Chey, A.J. Lembo, B.J. Lavins, and et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety Am J Gastroenterol 107 2012 1702 1712
159. J.E. Macdougall, J.M. Johnston, B.J. Lavins, and et al. An evaluation of the FDA responder endpoint for IBS-C clinical trials: analysis of data from linaclotide Phase 3 clinical trials Neurogastroenterol Motil 25 2013 481 486
160. J.M. Johnston, C.B. Kurtz, J.E. Macdougall, and et al. Linaclotide improves abdominal pain and bowel habits in a phase IIb study of patients with irritable bowel syndrome with constipation Gastroenterology 139 2010 1877 1886 e2
161. A.J. Lembo, C.B. Kurtz, J.E. Macdougall, and et al. Efficacy of linaclotide for patients with chronic constipation Gastroenterology 138 2010 886 895 e1
162. V. Andresen, M. Camilleri, I.A. Busciglio, and et al. Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome Gastroenterology 133 2007 761 768
163. P.B. Miner, R. Surowitz, R. Fogel, and et al. Plecanatide, a novel guanylate cyclase-C (GC-C) receptor agonist, is efficacious and safe in patients with chronic idiopathic constipation (CIC): results from a 951 patient, 12 week, multi-center trial Gastroenterology 144 Suppl 2013 S163
164. P. Miner, R. DeLuca, M. La Portilla, and et al. Plecanatide, a novel uroguanylin analog: a 12-week, randomized, double-blind, placebo-controlled, dose-ranging trial to evaluate efficacy and safety in patients with irritable bowel syndrome with constipation (IBS-C) Am J Gastroenterol 109 Suppl 2 2014 S541
165. A.G. Spencer, J.W. Jacobs, M.R. Leadbetter, and et al. RDX5791, a first-in-class minimally systemic NHE3 inhibitor in clinical development for CIC and IBS-C, increases intestinal sodium leading to enhanced intestinal fluid volume and transit Gastroenterology 140 Suppl 2011 S99
166. R.N. Appleby, and J.R. Walters The role of bile acids in functional GI disorders Neurogastroenterol Motil 26 2014 1057 1069
167. M. Camilleri, I. Busciglio, A. Acosta, and et al. Effect of increased bile acid synthesis or fecal excretion in irritable bowel syndrome-diarrhea Am J Gastroenterol 109 2014 1621 1630
168. B. Wong, M. Camilleri, S. McKinzie, and et al. Effects of A3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation Am J Gastroenterol 106 2011 2154 2164
169. W.D. Chey, M. Camilleri, L. Chang, and et al. A randomized placebo-controlled phase IIb trial of A3309, a bile acid transporter inhibitor, for chronic idiopathic constipation Am J Gastroenterol 106 2011 1803 1812
170. H. Buchwald, K.D. Rudser, S.E. Williams, and et al. Overall mortality, incremental life expectancy, and cause of death at 25 years in the program on the surgical control of the hyperlipidemias Ann Surg 251 2010 1034 1040
171. J.P. Jansen, D. Lorch, J. Langan, and et al. A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain J Pain 12 2011 185 193
172. G. Irving, J. Pénzes, B. Ramjattan, and et al. A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain J Pain 12 2011 175 184
173. W.D. Chey, L. Webster, M. Sostek, and et al. Naloxegol for opioid-induced constipation in patients with noncancer pain N Engl J Med 370 2014 2387 2396
174. L. Webster, S. Dhar, M. Eldon, and et al. A phase 2, double-blind, randomized, placebo-controlled, dose-escalation study to evaluate the efficacy, safety, and tolerability of naloxegol in patients with opioid-induced constipation Pain 154 2013 1542 1550
175. C.E. Sloots, A. Rykx, M. Cools, and et al. Efficacy and safety of prucalopride in patients with chronic noncancer pain suffering from opioid-induced constipation Dig Dis Sci 55 2010 2912 2921
176. B1. Cryer, S. Katz, R. Vallejo, and et al. A randomized study of lubiprostone for opioid-induced constipation in patients with chronic noncancer pain Pain Med 15 2014 1825 1834
177. M.M. Jamal, S.M. Mareya, F. Woldegeorgis, and et al. Lubiprostone significantly improves treatment response in non-methadone opioid-induced bowel dysfunction patients with chronic, non-cancer pain: results from a phase 3, randomized, double-blind, placebo-controlled clinical trial Gastroenterology 142 Suppl 1 2012 S144 S145
178. V. Palejwala, A. Ioshi, V. Patwa, and et al. SP-333, a D-amino acid containing peptide agonist of guanylate cyclase-C is a novel drug candidate for treatment of gastrointestinal disorders and diseases Am J Gastroenterol 109 Suppl 2 2014 S538
179. E. Corazziari Role of opioid ligands in the irritable bowel syndrome Can J Gastroenterol 13 Suppl A 1999 71A 75A
180. P.A. Cann, N.W. Read, C.D. Holdsworth, and et al. Role of loperamide and placebo in management of irritable bowel syndrome (IBS) Dig Dis Sci 29 1984 239 247
181. M.J. Smith, P. Cherian, G.S. Raju, and et al. Bile acid malabsorption in persistent diarrhoea J R Coll Physicians Lond 34 2000 448 451
182. N.J. Talley, S.F. Phillips, A. Haddad, and et al. GR 38032F (ondansetron), a selective 5HT3 receptor antagonist, slows colonic transit in healthy man Dig Dis Sci 35 1990 477 480
183. S. Gore, I.T. Gilmore, C.G. Haigh, and et al. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist Aliment Pharmacol Ther 4 1990 139 144
184. J.S. Scolapio, M. Camilleri, M.R. der Ohe, and et al. Ascending colon response to feeding: evidence for a 5-hydroxytryptamine-3 mechanism Scand J Gastroenterol 30 1995 562 567
185. R. Moynihan Alosetron: a case study in regulatory capture, or a victory for patients' rights? BMJ 325 2002 592 595
186. K. Garsed, J. Chernova, M. Hastings, and et al. A randomised trial of ondansetron for the treatment of irritable bowel syndrome with diarrhoea Gut 63 2014 1617 1625
187. T. Hirata, T. Funatsu, Y. Keto, and et al. Pharmacological profile of ramosetron, a novel therapeutic agent for IBS Inflammopharmacology 15 2007 5 9
188. T. Hirata, Y. Keto, M. Nakata, and et al. Effects of serotonin 5-HT3 receptor antagonists on stress-induced colonic hyperalgesia and diarrhoea in rats: a comparative study with opioid receptor agonists, a muscarinic receptor antagonist and a synthetic polymer Neurogastroenterol Motil 20 2008 557 565
189. K. Matsueda, S. Harasawa, M. Hongo, and et al. A phase II trial of the novel serotonin type 3 receptor antagonist ramosetron in Japanese male and female patients with diarrhea-predominant irritable bowel syndrome Digestion 77 2008 225 235
190. K. Matsueda, S. Harasawa, M. Hongo, and et al. A randomized, double-blind, placebo-controlled clinical trial of the effectiveness of the novel serotonin type 3 receptor antagonist ramosetron in both male and female Japanese patients with diarrhea-predominant irritable bowel syndrome Scand J Gastroenterol 43 2008 1202 1211
191. S. Fukudo, M. Ida, H. Akiho, and et al. Effect of ramosetron on stool consistency in male patients with irritable bowel syndrome with diarrhea: randomized and placebo-controlled trial Clin Gastroenterol Hepatol 12 2014 953 959
192. M. Grover, and M. Camilleri Invited editorial: ramosetron in irritable bowel syndrome with diarrhea: new hope or the same old story? Clin Gastroenterol Hepatol 12 2014 960 962
193. T. Chiba, K. Yamamoto, S. Sato, and et al. Long-term efficacy and safety of ramosetron in the treatment of diarrhea-predominant irritable bowel syndrome Clin Exp Gastroenterol 6 2013 123 128
194. K.J. Lee, N.Y. Kim, J.K. Kwon, and et al. Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine Neurogastroenterol Motil 23 2011 1098 1104
195. M. Pimentel, A. Lembo, W.D. Chey, S. Zakko, et al. TARGET Study Group Rifaximin therapy for patients with irritable bowel syndrome without constipation N Engl J Med 364 2011 22 32
196. S.B. Menees, M. Maneerattannaporn, H.M. Kim, and et al. The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta-analysis Am J Gastroenterol 107 2012 28 35
197. Lembo A, Pimentel M, Rao SS, et al. Efficacy and safety of repeat treatment with rifaximin for diarrhea-predominant irritable bowel syndrome (IBS-D): results of the TARGET 3 study. Presented at the American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course. Philadelphia, Pennsylvania, October 17-22, 2014.
198. L.S. Dove, A. Lembo, C.W. Randall, and et al. Eluxadoline benefits patients with irritable bowel syndrome with diarrhea in a phase 2 study Gastroenterology 145 2013 329 338
199. A. Lembo, S. Dove, D. Andrae, and et al. Eluxadoline for the treatment of diarrhea-predominant irritable bowel syndrome: results of 2 randomized, double-blind, placebo-controlled phase 3 clinical trials of efficacy and safety Gastroenterology 146 Suppl 1 2014 S159
200. J. Freiman, J. Jackson, K.S. Frazier, and et al. LX1031: inhibition of 5-HT synthesis as a new target in the management of irritable bowel syndrome (IBS) Neurogastroenterol Motil 21 2009 250
201. P.M. Brown, D.A. Drossman, A.J. Wood, and et al. The tryptophan hydroxylase inhibitor LX1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome Gastroenterology 141 2011 507 516
202. P. Holzer Tachykinin receptor antagonists: silencing neuropeptides with a role in the disturbed gut R. Spiller, D. Grundy, Pathophysiology of the Enteric Nervous System 2004 Blackwell London 212 227
203. A. Lecci, A. Capriati, and C.A. Maggi Tachykinin NK2 receptor antagonists for the treatment of irritable bowel syndrome Br J Pharmacol 141 2004 1249 1263
204. J.F. Tack, Y.S. Dochev, A. Bochenek, and et al. Efficacy of ibodutant, a selective antagonist of neurokinin 2 receptors, in irritable bowel syndrome with diarrhea (IBS-D): the results of a double-blind, randomized, placebo-controlled, parallel-group phase II study Gastroenterology 144 Suppl 1 2013 S92 S93
205. A.E. Bharucha, K. Ravi, and A.R. Zinsmeister Comparison of selective M3 and nonselective muscarinic receptor antagonists on gastrointestinal transit and bowel habits in humans Am J Physiol 299 2010 G215 G219
206. J. Czimmer, G. Süto, A. Király, and et al. Otilonium bromide enhances sensory thresholds of volume and pressure in patients with irritable bowel syndrome J Physiol Paris 95 2001 153 156
207. D. Krueger, K. Michel, S. Allam, and et al. Effect of hyoscine butylbromide (Buscopan®) on cholinergic pathways in the human intestine Neurogastroenterol Motil 25 2013 e530 e539
208. P. Clavé, M. Acalovschi, J.K. Triantafillidis OBIS Study Investigators Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome Aliment Pharmacol Ther 34 2011 432 442
209. F.Y. Chang, C.L. Lu, J.C. Luo, and et al. The evaluation of otilonium bromide treatment in Asian patients with irritable bowel syndrome J Neurogastroenterol Motil 17 2011 402 410
210. Y. Fukushima, H. Suzuki, J. Matsuzaki, and et al. Efficacy of solifenacin on irritable bowel syndrome with diarrhea: open-label prospective pilot trial J Neurogastroenterol Motil 18 2012 317 323
211. K. Anderson, and L. Fischer Prevention of GI absorption of bacterial toxins: an in vitro evaluation of the potential for prophylactic use of a novel oral adsorbent (AST-120) Gastroenterology 134 Suppl 1 2008 A-675
212. J.F. Tack, P.B. Miner Jr., L. Fischer, and et al. Randomised clinical trial: the safety and efficacy of AST-120 in non-constipating irritable bowel syndrome - a double-blind, placebo-controlled study Aliment Pharmacol Ther 34 2011 868 877
213. M. Guilarte, J. Santos, I. de Torres, and et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum Gut 56 2007 203 209
214. B. Lobo, M. Vicario, C. Martinez, and et al. Clinical benefit in IBS after disodium cromoglycate involves mast cell-mediated recovery of healthy-like innate immunity genes expression profile in the jejunal mucosa Gastroenterology 136 Suppl 1 2009 S156
215. B. Lobo, M. Vicario, C. Martinez, and et al. Clinical improvement in IBS after disodium cromoglycate involves mast cell-mediated toll-like receptor signaling downregulation Gastroenterology 140 Suppl 1 2011 499 500
216. O. Leri, S. Tubili, F.G. De Rosa, and et al. Management of diarrhoeic type of irritable bowel syndrome with exclusion diet and disodium cromoglycate Inflammopharmacology 5 1997 153 158
217. T.K. Klooker, B. Braak, K.E. Koopman, and et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome Gut 59 2010 1213 1221
218. R. Corinaldesi, V. Stanghellini, C. Cremon, and et al. Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof-of-concept study Aliment Pharmacol Ther 30 2009 245 252
219. C.N. Andrews, T.A. Griffiths, J. Kaufman, and et al. Mesalazine (5 aminosalicylic acid) alters faecal bacterial profiles, but not mucosal proteolytic activity in diarrhoea-predominant irritable bowel syndrome Aliment Pharmacol Ther 34 2011 374 383
220. A.E. Dorofeyev, E.A. Kiriyan, I.V. Vasilenko, and et al. Clinical, endoscopical and morphological efficacy of mesalazine in patients with irritable bowel syndrome Clin Exp Gastroenterol 4 2011 141 153
221. A.K. Tuteja, J.C. Fang, M. Al-Suqi, and et al. Double-blind placebo-controlled study of mesalamine in post-infective irritable bowel syndrome - a pilot study Scand J Gastroenterol 47 2012 1159 1164
222. C. Lam, W. Tan, M. Leighton, and et al. A multi-centre, parallel group, randomised placebo controlled trial of mesalazine for treatment of diarrhoea-predominant irritable bowel syndrome (IBS-D) Gastroenterology 146 Suppl 1 2014 S123 S124
223. G. Barbara, C. Cremon, L. Bellacosa, and et al. Randomized placebo controlled multicenter trial of mesalazine in patients with irritable bowel syndrome (IBS) Gastroenterology 146 Suppl 1 2014 S124
224. J.R. Walters, I.M. Johnston, J.D. Nolan, and et al. The response of patients with bile acid diarrhoea to the farnesoid X receptor agonist obeticholic acid Aliment Pharmacol Ther 41 2015 54 64
225. M. Camilleri, K. Lasch, and W. Zhou Irritable bowel syndrome: methods, mechanisms, and pathophysiology. The confluence of increased permeability, inflammation, and pain in irritable bowel syndrome Am J Physiol 303 2012 G775 G785
226. Q. Zhou, W.W. Souba, C.M. Croce, and et al. MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome Gut 59 2010 775 784
227. S. Basra, G.N. Verne, and Q. Zhou Randomized placebo-controlled trial of glutamine for the treatment of diarrhea-predominant irritable bowel syndrome Gastroenterology 144 Suppl 2013 S160
228. L. Chang, A. Lembo, and S. Sultan American Gastroenterological Association Institute technical review on the pharmacological management of irritable bowel syndrome Gastroenterology 147 2014 1149 1172
229. A.C. Ford, P. Moayyedi, B.E. Lacy, et al. Task Force on the Management of Functional Bowel Disorders American College of Gastroenterology monograph on the management of irritable bowel syndrome and chronic idiopathic constipation Am J Gastroenterol 109 Suppl 1 2014 S2 S26
230. T. Poynard, C. Regimbeau, and Y. Benhamou Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome Aliment Pharmacol Ther 15 2001 355 361
231. A.C. Ford, N.J. Talley, B.M. Spiegel, and et al. Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis BMJ 337 2008 a2313
232. W.D. Chey, A.J. Lembo, B.Y. Lavins, and et al. Linaclotide for irritable bowel syndrome with constipation: a 26-week, randomized, double-blind, placebo-controlled trial to evaluate efficacy and safety Am J Gastroenterol 107 2012 1702 1712
233. L. Ruepert, A.O. Quartero, N.J. de Wit, and et al. Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome Cochrane Database Syst Rev 8 2011 Aug 10 CD003460
234. A.C. Ford, E.M. Quigley, B.E. Lacy, and et al. Effect of antidepressants and psychological therapies, including hypnotherapy, in irritable bowel syndrome: systematic review and meta-analysis Am J Gastroenterol 109 2014 1350 1365
235. D.S. Weinberg, W. Smalley, J.J. Heidelbaugh, and et al. American Gastroenterological Association Institute Guideline on the pharmacological management of irritable bowel syndrome Gastroenterology 147 2014 1146 1148
236. L.A. Houghton, C. Fell, P.J. Whorwell, and et al. Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome Gut 56 2007 1218 1225
237. S. van Wanrooij, M.M. Wouters, L. Van Oudenhove, and et al. Effect of the H1-receptor antagonist ebastin on visceral perception and clinical symptoms in IBS Gastroenterology 144 Suppl 1 2013 S160
238. R. Sood, G.R. Law, and A.C. Ford Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or 'psychomarkers'? Nat Rev Gastroenterol Hepatol 11 2014 683 691
239. M. Corsetti, L. Van Oudenhove, and J. Tack The quest for biomarkers in IBS - where should it lead us? Neurogastroenterol Motil 26 2014 1669 1676
240. G. Barbara IBS: biomarkers for IBS: ready for prime time? Nat Rev Gastroenterol Hepatol 12 2015 9 10
241. Biomarkers Definitions Working Group Biomarkers and surrogate endpoints: preferred definitions and conceptual framework Clin Pharmacol Ther 69 2001 89 95
242. M. Camilleri, A. Acosta, I. Busciglio, and et al. Effect of colesevelam on fecal bile acids and bowel functions in diarrhea-predominant irritable bowel syndrome Aliment Pharmacol Ther 41 2015 438 448
243. M.R. Briejer, G.J. Veen, L.M. Akkermans, and et al. Cisapride and structural analogs selectively enhance 5-hydroxytryptamine (5-HT)-induced purinergic neurotransmission in the guinea pig proximal colon J Pharmacol Exp Ther 274 1995 641 648
244. R. Morphy, C. Kay, and Z. Rankovic From magic bullets to designed multiple ligands Drug Discov Today 9 2004 641 651
245. M. Camilleri, A.R. Northcutt, S. Kong, G.E. Dukes, D. McSorley, and A.W. Mangel Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial Lancet 355 2000 1035 1040
246. M. Camilleri, L. Bueno, F. De Ponti, and et al. Pharmacological and pharmacokinetic aspects of functional gastrointestinal disorders Gastroenterology 130 2006 1421 1434
247. F. Shanahan, and E.M. Quigley Manipulation of the microbiota for treatment of IBS and IBD - challenges and controversies Gastroenterology 146 2014 1554 1563
248. E.A. Mayer, T. Savidge, and R.J. Shulman Brain-gut microbiome interactions and functional bowel disorders Gastroenterology 146 2014 1500 1512
249. M.W. Musch, Y. Wang, E.C. Claud, and E.B. Chang Lubiprostone decreases mouse colonic inner mucus layer thickness and alters intestinal microbiota Dig Dis Sci 58 2013 668 677
250. S. Keely, C.J. Kelly, T. Weissmueller, A. Burgess, and et al. Activated fluid transport regulates bacterial-epithelial interactions and significantly shifts the murine colonic microbiome Gut Microbes 3 2012 250 260
251. H. Hao, X. Zheng, and G. Wang Insights into drug discovery from natural medicines using reverse pharmacokinetics Trends Pharmacol Sci 35 2014 168 177
252. F. Cremonini Standardized herbal treatments on functional bowel disorders: moving from putative mechanisms of action to controlled clinical trials Neurogastroenterol Motil 26 2014 893 900
253. E.C. Chow, and K.S. Pang Why we need proper PBPK models to examine intestine and liver oral drug absorption Curr Drug Metab 14 2013 57 79
254. X. Zhang, and W. Wu Ligand-mediated active targeting for enhanced oral absorption Drug Discov Today 19 2014 898 904
255. F. De Ponti, E. Poluzzi, and N. Montanaro Organising evidence on QT prolongation and occurrence of Torsades de Pointes with non-antiarrhythmic drugs: a call for consensus Eur J Clin Pharmacol 57 2001 185 209
256. F. De Ponti, E. Poluzzi, A. Cavalli, and et al. Safety of non-antiarrhythmic drugs that prolong the QT interval or induce torsade de pointes: an overview Drug Saf 25 2002 263 286
257. W.E. Evans, and M.V. Relling Pharmacogenomics: translating functional genomics into rational therapeutics Science 286 1999 487 491
258. H.-G. Xie, R.B. Kim, A.J.J. Wood, and et al. Molecular basis of ethnic differences in drug disposition and response Annu Rev Pharmacol Toxicol 41 2001 815 850
259. Q.Y. Yue, Z.H. Zhong, G. Tybring, and et al. Pharmacokinetics of nortriptyline and its 10-hydroxy metabolite in Chinese subjects of different CYP2D6 genotypes Clin Pharmacol Ther 64 1998 384 390
260. E. Aklillu, I. Persson, L. Bertilsson, and et al. Frequent distribution of ultrarapid metabolizers of debrisoquine in an Ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles J Pharmacol Exp Ther 278 1996 441 446
261. R.C. Givens, and P.B. Watkins Pharmacogenetics and clinical gastroenterology Gastroenterology 125 2003 240 248
262. A.C. Ford, N.J. Talley, P.S. Schoenfeld, and et al. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis Gut 58 2009 367 378
263. J.P. Zhang, and A.K. Malhotra Pharmacogenetics and antipsychotics: therapeutic efficacy and side effects prediction Exp Opin Drug Metab Toxicol 7 2011 9 37
264. Y. Li, Y. Jie, J. Xie, and et al. The association of serotonin transporter genetic polymorphisms and irritable bowel syndrome and its influence on tegaserod treatment in Chinese patients Dig Dis Sci 52 2000 2942 2949
265. B.S. Wong, M. Camilleri, P.J. Carlson, and et al. A Klothoß variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea Gastroenterology 140 2011 1934 1942
266. A.S. Rao, B.S. Wong, M. Camilleri, and et al. Chenodeoxycholate in females with IBS-constipation: a pharmacodynamic and pharmacogenetic analysis Gastroenterology 139 2010 1549 1558
267. B.S. Wong, M. Camilleri, P.J. Carlson, and et al. Pharmacogenetics of the effects of colesevelam on colonic transit in IBS with diarrhea Dig Dis Sci 57 2012 1222 1226
268. M. Camilleri Physiological underpinnings of irritable bowel syndrome: neurohormonal mechanisms J Physiol 592 2014 2967 2980
269. M. Camilleri Opioid-induced constipation: challenges and therapeutic opportunities Am J Gastroenterol 106 2011 835 842 quiz 843