IBS and the role of otilonium bromide

International Journal of Colorectal Disease

Volumn 28, Issue 3, 2013, Pages 295-304

  Boeckxstaens, Guy ^a   Corazziari, Enrico S ^b   Mearin, Fermín ^c   Tack, Jan ^a  

^a UNIVERSITY HOSPITALS LEUVEN   (Belgium)

^b SAPIENZA UNIVERSITY OF ROME   (Italy)

^c CENTRO MÉDICO TEKNON   (Spain)

Author keywords

Irritable bowel disorder; Irritable bowel syndrome; Otilonium bromide; Spasmolytics

Indexed keywords

ALOSETRON; AMITRIPTYLINE; ANTIDEPRESSANT AGENT; BIOLOGICAL MARKER; CHOLINERGIC RECEPTOR BLOCKING AGENT; CILANSETRON; CIMETROPIUM; DESIPRAMINE; DICYCLOVERINE; HYOSCYAMINE; LINACLOTIDE; LOPERAMIDE; LUBIPROSTONE; MEBEVERINE; OTILONIUM BROMIDE; PEPPERMINT OIL; PINAVERIUM BROMIDE; PLACEBO; PRIFINIUM BROMIDE; PROBIOTIC AGENT; PRUCALOPRIDE; RIFAXIMIN; SPASMOLYTIC AGENT; TEGASEROD;

ABDOMINAL DISTENSION; ABDOMINAL PAIN; ANTICHOLINERGIC EFFECT; BLOATING; CLINICAL FEATURE; COGNITIVE THERAPY; CONSTIPATION; DEFECATION DISORDER; DIARRHEA; DIET THERAPY; DISEASE ACTIVITY; DISEASE SEVERITY; DRUG EFFICACY; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG TOLERABILITY; ECONOMIC ASPECT; FLATULENCE; HUMAN; HYPNOSIS; INCIDENCE; IRRITABLE COLON; LIFESTYLE MODIFICATION; LONG TERM CARE; LOW DRUG DOSE; NAUSEA; PATHOPHYSIOLOGY; PREVALENCE; PRIORITY JOURNAL; QUALITY OF LIFE; RECURRENCE RISK; RECURRENT DISEASE; REVIEW; RISK ASSESSMENT; RISK FACTOR; SOCIAL ASPECT; SUPPLEMENTATION; TACHYCARDIA; VISUAL IMPAIRMENT; XEROSTOMIA;

CLINICAL TRIALS AS TOPIC; COST OF ILLNESS; GASTROINTESTINAL AGENTS; HUMANS; IRRITABLE BOWEL SYNDROME; PARASYMPATHOLYTICS; QUATERNARY AMMONIUM COMPOUNDS;

EID: 84879464577     PISSN: 01791958     EISSN: 14321262     Source Type: Journal    
DOI: 10.1007/s00384-012-1598-0     Document Type: Review

References (97)

1. Mearin F, Badia X, Balboa A, Baro E, Caldwell E, Cucala M, Diaz-Rubio M, Fueyo A, Ponce J, Roset M, Talley NJ (2001) Irritable bowel syndrome prevalence varies enormously depending on the employed diagnostic criteria: comparison of Rome II versus previous criteria in a general population. Scand J Gastroenterol 36:1155-1161 (Pubitemid 32917583)
2. Saito YA, Schoenfeld P, Locke GR (2002) The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol 97:1910-1915
3. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC (2006) Functional bowel disorders. Gastroenterology 130:1480-1491
4. Sperber AD, Shvartzman P, Friger M, Fich A (2007) A comparative reappraisal of the Rome II and Rome III diagnostic criteria: are we getting closer to the 'true' prevalence of irritable bowel syndrome? Eur J Gastroenterol Hepatol 19:441-447 (Pubitemid 46725749)
5. Choung RS, Locke GR (2011) Epidemiology of IBS. Gastroenterol Clin North Am 40:1-10
6. Longstreth GF, Wolde-Tsadik G (1993) Irritable bowel-type symptoms in HMO examinees. Prevalence, demographics, and clinical correlates. Dig Dis Sci 38:1581-1589 (Pubitemid 23271410)
7. Russo MW, Gaynes BN, Drossman DA (1999) A national survey of practice patterns of gastroenterologists with comparison to the past two decades. J Clin Gastroenterol 29:339-343
8. Drossman DA, Thompson WG (1992) The irritable bowel syndrome: review and a graduated multicomponent treatment approach. Ann Intern Med 116:1009-1016
9. Lembo A, Ameen VZ, Drossman DA (2005) Irritable bowel syndrome: toward an understanding of severity. Clin Gastroenterol Hepatol 3(8):717-725 (Pubitemid 41116722)
10. Sandler RS, Everhart JE, Donowitz M, Adams E, Cronin K, Goodman C, Gemmen E, Shah S, Avdic A, Rubin R (2002) The burden of selected digestive diseases in the United States. Gastroenterology 122:1500-1511 (Pubitemid 34465190)
11. Hollowell J, Lundgren A, Johansson S (2002) Irritable bowel syndrome: patterns of ambulatory health care and resource use in the United States, 1993-1997. Dig Dis Sci 47:1115-1121 (Pubitemid 34439191)
12. Inadomi JM, Fennerty MB, Bjorkman D (2003) Systematic review: the economic impact of irritable bowel syndrome. Aliment Pharmacol Ther 18:671-682 (Pubitemid 37271832)
13. Hillila MT, Farkkila NJ, Farkkila MA (2010) Societal costs for irritable bowel syndrome - a population based study. Scand J Gastroenterol 45:582-591
14. Johansson PA, Farup PG, Bracco A, Vandvik PO (2010) How does comorbidity affect cost of health care in patients with irritable bowel syndrome? A cohort study in general practice. BMC Gastroenterol 10:31
15. Longstreth GF, Yao JF (2004) Irritable bowel syndrome and surgery: a multivariable analysis. Gastroenterology 126:1665-1673
16. Chang JY, Locke GR, McNally MA, Halder SL, Schleck CD, Zinsmeister AR, Talley NJ (2010) Impact of functional gastrointestinal disorders on survival in the community. Am J Gastroenterol 105:822-832
17. Norgaard M, Farkas DK, Pedersen L, Erichsen R, de la Cour ZD, Gregersen H, Sorensen HT (2011) Irritable bowel syndrome and risk of colorectal cancer: a Danish nationwide cohort study. Br J Cancer 104:1202-1206
18. Spiegel B, Schoenfeld P, Naliboff B (2007) Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther 26:183-193 (Pubitemid 46985489)
19. Hammer J, Eslick GD, Howell SC, Altiparmak E, Talley NJ (2004) Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut 53:666-672 (Pubitemid 38561444)
20. Delvaux M (2002) Role of visceral sensitivity in the pathophysiology of irritable bowel syndrome. Gut 51(Suppl 1):i67-i71
21. Camilleri M (2009) Genetics and irritable bowel syndrome: from genomics to intermediate phenotype and pharmacogenetics. Dig Dis Sci 54:2318-2324
22. Ohman L, Simren M (2010) Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 7:163-173
23. Camilleri M (1999) Motor function in irritable bowel syndrome. Can J Gastroenterol 13(Suppl A):8A-11A
24. Barbara G, Stanghellini V (2009) Biomarkers in IBS: when will they replace symptoms for diagnosis and management? Gut 58:1571-1575
25. Azpiroz F (2005) Intestinal gas dynamics: mechanisms and clinical relevance. Gut 54:893-895 (Pubitemid 40873894)
26. Kuiken SD, Lindeboom R, Tytgat GN, Boeckxstaens GE (2005) Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 22:157-164 (Pubitemid 41039704)
27. Mertz H, Naliboff B, Munakata J, Niazi N, Mayer EA (1995) Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology 109:40-52
28. Lembo T, Munakata J, Mertz H, Niazi N, Kodner A, Nikas V, Mayer EA (1994) Evidence for the hypersensitivity of lumbar splanchnic afferents in irritable bowel syndrome. Gastroenterology 107:1686-1696 (Pubitemid 24357622)
29. Elsenbruch S, Rosenberger C, Enck P, Forsting M, Schedlowski M, Gizewski ER (2010) Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study. Gut 59:489-495
30. Blankstein U, Chen J, Diamant NE, Davis KD (2010) Altered brain structure in irritable bowel syndrome: potential contributions of pre-existing and disease-driven factors. Gastroenterology 138:1783-1789
31. Seminowicz DA, Labus JS, Bueller JA, Tillisch K, Naliboff BD, Bushnell MC, Mayer EA (2010) Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology 139:48-57.e2
32. Elsenbruch S (2011) Abdominal pain in irritable bowel syndrome: a review of putative psychological, neural and neuro-immune mechanisms. Brain Behav Immun 25:386-394
33. Gwee KA, Collins SM, Read NW, Rajnakova A, Deng Y, Graham JC, McKendrick MW, Moochhala SM (2003) Increased rectal mucosal expression of interleukin 1beta in recently acquired post-infectious irritable bowel syndrome. Gut 52:523-526 (Pubitemid 36363405)
34. Spiller RC, Jenkins D, Thornley JP, Hebden JM, Wright T, Skinner M, Neal KR (2000) Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 47:804-811
35. Guilarte M, Santos J, de Torres I, Alonso C, Vicario M, Ramos L, Martinez C, Casellas F, Saperas E, Malagelada JR (2007) Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut 56:203-209
36. Barbara G, Wang B, Stanghellini V, de Giorgio R, Cremon C, Di Nardo G, Trevisani M, Campi B, Geppetti P, Tonini M, Bunnett NW, Grundy D, Corinaldesi R (2007) Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology 132:26-37 (Pubitemid 46108761)
37. Bueno L, Fioramonti J (2002) Visceral perception: inflammatory and non-inflammatory mediators. Gut 51(Suppl 1):i19-i23
38. Azpiroz F, Bouin M, Camilleri M, Mayer EA, Poitras P, Serra J, Spiller RC (2007) Mechanisms of hypersensitivity in IBS and functional disorders. Neurogastroenterol Motil 19:62-88 (Pubitemid 46058983)
39. Cenac N, Andrews CN, Holzhausen M, Chapman K, Cottrell G, Andrade-Gordon P, Steinhoff M, Barbara G, Beck P, Bunnett NW, Sharkey KA, Ferraz JG, Shaffer E, Vergnolle N (2007) Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest 117:636-647 (Pubitemid 46348522)
40. Klooker TK, Braak B, Koopman KE, Welting O, Wouters MM, van der Heide S, Schemann M, Bischoff SC, van den Wijngaard RM, Boeckxstaens GE (2010) The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut 59:1213-1221
41. Soderholm JD, Yang PC, Ceponis P, Vohra A, Riddell R, Sherman PM, Perdue MH (2002) Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine. Gastroenterology 123:1099-1108
42. Zhou Q, Souba WW, Croce CM, Verne GN (2010) MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut 59:775-784
43. Piche T, Barbara G, Aubert P, Bruley des Varannes S, Dainese R, Nano JL, Cremon C, Stanghellini V, De Giorgio R, Galmiche JP, Neunlist M (2009) Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut 58:196-201
44. Gecse K, Roka R, Ferrier L, Leveque M, Eutamene H, Cartier C, Ait-Belgnaoui A, Rosztoczy A, Izbeki F, Fioramonti J, Wittmann T, Bueno L (2008) Increased faecal serine protease activity in diarrhoeic IBS patients: a colonic lumenal factor impairing colonic permeability and sensitivity. Gut 57:591-599 (Pubitemid 351579969)
45. Lee KJ, Tack J (2010) Altered intestinal microbiota in irritable bowel syndrome. Neurogastroenterol Motil 22:493-498
46. Thomas KB (1987) General practice consultations: is there any point in being positive? Br Med J 294:1200-1202 (Pubitemid 17070676)
47. Brenner DM, Moeller MJ, Chey WD, Schoenfeld PS (2009) The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol 104:1033-1049, quiz 1050
48. Hoveyda N, Heneghan C, Mahtani KR, Perera R, Roberts N, Glasziou P (2009) A systematic review and meta-analysis: probiotics in the treatment of irritable bowel syndrome. BMC Gastroenterol 9:15
49. Cadau G, Pallotta D, Badiali D, Corazziari E (1998) L'impiego degli antidepressivi triciclici a basso dosaggio nel trattamento dei disturbi funzionali del tratto gastrointestinal superior ed inferiore. Neurogastroenterologica 4:16-20
50. Drossman DA, Camilleri M, Mayer EA, Whitehead WE (2002) AGA technical review on irritable bowel syndrome. Gastroenterology 123:2108-2131 (Pubitemid 35408332)
51. Ford AC, Talley NJ, Schoenfeld PS, Quigley EM, Moayyedi P (2009) Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58:367-378
52. Pimentel M, Lembo A, Chey WD, Zakko S, Ringel Y, Yu J, Mareya SM, Shaw AL, Bortey E, Forbes WP (2011) Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 364:22-32
53. Krause R, Ameen V, Gordon SH, West M, Heath AT, Perschy T, Carter EG (2007) A randomized, double-blind, placebo-controlled study to assess efficacy and safety of 0.5 mg and 1 mg alosetron in women with severe diarrhea-predominant IBS. Am J Gastroenterol 102:1709-1719 (Pubitemid 47206697)
54. Olden KW, Crowell MD (2005) Cilansetron. Drugs Today (Barc) 41:661-666 (Pubitemid 43074775)
55. Agrawal A, Houghton LA, Morris J, Reilly B, Guyonnet D, Goupil Feuillerat N, Schlumberger A, Jakob S, Whorwell PJ (2009) Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther 29:104-114
56. Sakai T, Makino H, Ishikawa E, Oishi K, Kushiro A (2011) Fermented milk containing Lactobacillus casei strain Shirota reduces incidence of hard or lumpy stools in healthy population. Int J Food Sci Nutr 62:423-430
57. Corazziari E, Badiali D, Bazzocchi G, Bassotti G, Roselli P, Mastropaolo G, Luca MG, Galeazzi R, Peruzzi E (2000) Long term efficacy, safety, and tolerabilitity of low daily doses of isosmotic polyethylene glycol electrolyte balanced solution (PMF-100) in the treatment of functional chronic constipation. Gut 46:522-526 (Pubitemid 30305817)
58. Ford AC, Suares NC (2011) Effect of laxatives and pharmacological therapies in chronic idiopathic constipation: systematic review and meta-analysis. Gut 60:209-218
59. Drossman DA, Chey W, Panas R, Wahle A, Scott C, Ueno R (2007) Lubiprostone significantly improves symptom relief rates in adults with irritable bowel syndrome and constipation (IBS-C): data from two twelve-week, randomized, placebo-controlled, double-blind trials. Gastroenterology & Hepatology 132:2586-2587
60. American College of Gastroenterology Functional Gastrointestinal Disorders Task Force (2002) Evidence-based position statement on the management of irritable bowel syndrome in North America. Am J Gastroenterol 97:S1-S5
61. Whorwell PJ, Prior A, Colgan SM (1987) Hypnotherapy in severe irritable bowel syndrome: further experience. Gut 28:423-425 (Pubitemid 17056876)
62. Toner BB (2005) Cognitive-behavioral treatment of irritable bowel syndrome. CNS Spectr 10:883-890 (Pubitemid 41784933)
63. Madisch A, Holtmann G, Plein K, Hotz J (2004) Treatment of irritable bowel syndrome with herbal preparations: results of a double-blind, randomized, placebo-controlled, multi-centre trial. Aliment Pharmacol Ther 19:271-279 (Pubitemid 38253501)
64. Leung WK, Wu JC, Liang SM, Chan LS, Chan FK, Xie H, Fung SS, Hui AJ, Wong VW, Che CT, Sung JJ (2006) Treatment of diarrhea-predominant irritable bowel syndrome with traditional Chinese herbal medicine: a randomized placebo-controlled trial. Am J Gastroenterol 101:1574-1580 (Pubitemid 43980632)
65. Scarpignato C, Pelosini I (1999) Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. Can J Gastroenterol 13(Suppl A):50A-65A
66. Tack J, Fried M, Houghton LA, Spicak J, Fisher G (2006) Systematic review: the efficacy of treatments for irritable bowel syndrome - a European perspective. Aliment Pharmacol Ther 24:183-205 (Pubitemid 43972890)
67. Brandt LJ, Bjorkman D, Fennerty MB, Locke GR, Olden K, Peterson W, Quigley E, Schoenfeld P, Schuster M, Talley N (2002) Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol 97:S7-S26
68. Wheatley D (1976) Irritable colon syndrome treated with an antispasmodic drug. Practitioner 217:276-280
69. Page JG, Dirnberger GM (1981) Treatment of the irritable bowel syndrome with Bentyl (dicyclomine hydrochloride). J Clin Gastroenterol 3:153-156 (Pubitemid 11113503)
70. Ritchie JA, Truelove SC (1979) Treatment of irritable bowel syndrome with lorazepam, hyoscine butylbromide, and ispaghula husk. Br Med J 1:376-378 (Pubitemid 9095236)
71. Dobrilla G, Imbimbo BP, Piazzi L, Bensi G (1990) Longterm treatment of irritable bowel syndrome with cimetropium bromide: a double blind placebo controlled clinical trial. Gut 31:355-358 (Pubitemid 20093680)
72. Centonze V, Imbimbo BP, Campanozzi F, Attolini E, Daniotti S, Albano O (1988) Oral cimetropium bromide, a new antimuscarinic drug, for long-term treatment of irritable bowel syndrome. Am J Gastroenterol 83:1262-1266
73. Piai G, Visconti M, Imbimbo BP (1987) Long-term treatment of irritable bowel syndrome with cimetropium bromide, a new antimuscarinic compound. Curr Ther Res 41:967-977 (Pubitemid 17089795)
74. Kruis W, Weinzierl M, Schussler P, Holl J (1986) Comparison of the therapeutic effect of wheat bran, mebeverine and placebo in patients with the irritable bowel syndrome. Digestion 34:196-201 (Pubitemid 16064246)
75. Baldi F, Longanesi A, Blasi A, Monello S, Cestari R, Missale G, Corazziari E, Badiali G, Pescatori M, Anastasio G et al (1991) Clinical and functional evaluation of the efficacy of otilonium bromide: a multicenter study in Italy. Ital J Gastroenterol 23:60-63
76. Battaglia G, Morselli-Labate AM, Camarri E, Francavilla A, De Marco F, Mastropaolo G, Naccarato R (1998) Otilonium bromide in irritable bowel syndrome: a double-blind, placebo-controlled, 15-week study. Aliment Pharmacol Ther 12:1003-1010 (Pubitemid 28454384)
77. Awad R, Dibildox M, Ortiz F (1995) Irritable bowel syndrome treatment using pinaverium bromide as a calcium channel blocker. A randomized double-blind placebo-controlled trial. Acta Gastroenterol Latinoam 25:137-144
78. Gilvarry J, Kenny A, Fielding JF (1989) The non-effect of pirenzepine in dietary resistant irritable bowel syndrome. Ir J Med Sci 158:262 (Pubitemid 20054444)
79. Ghidini O, Saponati G, Intrieri L (1986) Single drug treatment for irritable colon: rociverine versus trimebutine maleate. Curr Ther Res 39:541-548 (Pubitemid 17027296)
80. Irvine EJ, Whitehead WE, Chey WD, Matsueda K, Shaw M, Talley NJ, Veldhuyzen van Zanten SJ (2006) Design of treatment trials for functional gastrointestinal disorders. Gastroenterology 130:1538-1551
81. Quartero AO, Meineche-Schmidt V, Muris J, Rubin G, de Wit N (2005) Bulking agents, antispasmodic and antidepressant medication for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev:CD003460
82. Lesbros-Pantoflickova D, Michetti P, Fried M, Beglinger C, Blum AL (2004) Meta-analysis: the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 20:1253-1269 (Pubitemid 40040072)
83. Poynard T, Regimbeau C, Benhamou Y (2001) Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 15:355-361 (Pubitemid 32187557)
84. Poynard T, Naveau S, Mory B, Chaput JC (1994) Meta-analysis of smooth muscle relaxants in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 8:499-510 (Pubitemid 24324487)
85. Ford AC, Talley NJ, Spiegel BM, Foxx-Orenstein AE, Schiller L, Quigley EM, Moayyedi P (2008) Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 337:a2313
86. Sutton JA, Kilminster SG, Mould GP (1997) The clinical pharmacology of single doses of otilonium bromide in healthy volunteers. Eur J Clin Pharmacol 52:365-369 (Pubitemid 27341936)
87. Evangelista S, Cochet P, Bromet N, Criscuoli M, Maggi CA (2000) A distribution study with (14)C-otilonium bromide in the rat: evidence for selective tropism for large intestine after oral administration. Drug Metab Dispos 28:643-647 (Pubitemid 30390402)
88. Evangelista S (1999) Otilonium bromide: a selective spasmolytic for the gastrointestinal tract. J Int Med Res 27:207-222 (Pubitemid 30064249)
89. Maggi CA, Manzini S, Meli A (1983) Octylonium bromide: a smooth muscle relaxant which interferes with calcium ions mobilization. Arch Int Pharmacodyn Ther 264:305-323 (Pubitemid 13050103)
90. Santicioli P, Zagorodnyuk V, Renzetti AR, Maggi CA (1999) Antimuscarinic, calcium channel blocker and tachykinin NK2 receptor antagonist actions of otilonium bromide in the circular muscle of guinea-pig colon. Naunyn Schmiedebergs Arch Pharmacol 359:420-427 (Pubitemid 29252284)
91. Strege PR, Evangelista S, Lyford GL, Sarr MG, Farrugia G (2004) Otilonium bromide inhibits calcium entry through L-type calcium channels in human intestinal smooth muscle. Neurogastroenterol Motil 16:167-173 (Pubitemid 38580961)
92. Strege PR, Sha L, Beyder A, Bernard CE, Perez-Reyes E, Evangelista S, Gibbons SJ, Szurszewski JH, Farrugia G (2010) T-type Ca(2+) channel modulation by otilonium bromide. Am J Physiol Gastrointest Liver Physiol 298:G706-G713
93. Gallego D, Auli M, Aleu J, Martínez E, Rofes L, Marti-Ragué J, Jiménez M, Clavé P (2010) Effect of otilonium bromide on contractile patterns in the human sigmoid colon. Neurogastroenterol Motil 22:e180-e191
94. Glende M, Morselli-Labate AM, Battaglia G, Evangelista S (2002) Extended analysis of a double-blind, placebo-controlled, 15-week study with otilonium bromide in irritable bowel syndrome. Eur J Gastroenterol Hepatol 14:1331-1338 (Pubitemid 36054922)
95. Clavé P, Acalovschi M, Triantafillidis JK, Uspensky YP, Kalayci C, Shee V, Tack J (2011) 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 34:432-442
96. Evangelista S (2012) Benefits from long-term treatment in irritable bowel syndrome. Gastroenterol Res Pract 2012:936-960
97. Simrén M (2009) Bloating and abdominal distention: not so poorly understood anymore! Gastroenterology 136(5):1487-1490