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Reviews

Investigational agents for the irritable bowel syndrome

, MD, , MD, , MD & , MD FACG AGAF
Pages 1161-1178 | Published online: 13 Sep 2010

Bibliography

  • Brandt LJ, Bjorkman D, Fennerty MB, Systematic review on the management of irritable bowel syndrome in North America. Am J Gastroenterol 2002;97(11 Suppl):S7-26
  • Gralnek IM, Hays RD, Kilbourne A, The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology 2000;119(3):654-60
  • Eglen RM, Hegde SS, Watson N. Muscarinic receptor subtypes and smooth muscle function. Pharmacol Rev 1996;48(4):531-65
  • Matsui M, Motomura D, Karasawa H, Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype. Proc Natl Acad Sci USA 2000;97(17):9579-84
  • Akehurst R, Kaltenthaler E. Treatment of irritable bowel syndrome: a review of randomised controlled trials. Gut 2001;48(2):272-82
  • Ford AC, Talley NJ, Spiegel BM, Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta-analysis. BMJ 2008;337:a2313
  • Kobayashi S, Ikeda K, Suzuki M, Effects of YM905, a novel muscarinic M3-receptor antagonist, on experimental models of bowel dysfunction in vivo. Jpn J Pharmacol 2001;86(3):281-8
  • Houghton LA, Rogers J, Whorwell PJ, Zamifenacin (UK-76, 654) a potent gut M3 selective muscarinic antagonist, reduces colonic motor activity in patients with irritable bowel syndrome. Aliment Pharmacol Ther 1997;11(3):561-8
  • Talley NJ. Serotoninergic neuroenteric modulators. Lancet 2001;358(9298):2061-8
  • Wade PR, Chen J, Jaffe B, Localization and function of a 5-HT transporter in crypt epithelia of the gastrointestinal tract. J Neurosci 1996;16(7):2352-64
  • Coates MD, Mahoney CR, Linden DR, Molecular defects in mucosal serotonin content and decreased serotonin reuptake transporter in ulcerative colitis and irritable bowel syndrome. Gastroenterology 2004;126(7):1657-64
  • Atkinson W, Lockhart S, Whorwell PJ, Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome. Gastroenterology 2006;130(1):34-43
  • Chen JJ, Li Z, Pan H, Maintenance of serotonin in the intestinal mucosa and ganglia of mice that lack the high-affinity serotonin transporter: abnormal intestinal motility and the expression of cation transporters. J Neurosci 2001;21(16):6348-61
  • Humphrey PP, Bountra C, Clayton N, Kozlowski K. Review article: the therapeutic potential of 5-HT3 receptor antagonists in the treatment of irritable bowel syndrome. Aliment Pharmacol Ther 1999;13(Suppl 2):31-8
  • Mangel AW, Northcutt AR. Review article: the safety and efficacy of alosetron, a 5-HT3 receptor antagonist, in female irritable bowel syndrome patients. Aliment Pharmacol Ther 1999;13(Suppl 2):77-82
  • Camilleri M, Northcutt AR, Kong S, Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo-controlled trial. Lancet 2000;355(9209):1035-40
  • Office of Post-Marketing Drug Risk Assessment F. Memorandum accessible through the Freedom of Information Act
  • Available from: www.fda.gov/ohrms/dockets/ac/02/transcripts/3848T1.pdf. [Cited 30 August 2002]
  • Muller-Lissner SA, Fumagalli I, Bardhan KD, Tegaserod, a 5-HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther 2001;15(10):1655-66
  • Kellow J, Lee OY, Chang FY, 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 2003;52(5):671-6
  • Evans BW, Clark WK, Moore DJ, Whorwell PJ. Tegaserod for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev 2004;(1):CD003960
  • Staniforth DH, Pennick M. Human pharmacology of renzapride: a new gastrokinetic benzamide without dopamine antagonist properties. Eur J Clin Pharmacol 1990;38(2):161-4
  • Song CW, Lee KY, Kim CD, Effect of cisapride and renzapride on gastrointestinal motility and plasma motilin concentration in dogs. J Pharmacol Exp Ther 1997;281(3):1312-16
  • Tack J, Middleton SJ, Horne MC, Pilot study of the efficacy of renzapride on gastrointestinal motility and symptoms in patients with constipation-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2006;23(11):1655-65
  • Camilleri M, McKinzie S, Fox J, Effect of renzapride on transit in constipation-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2004;2(10):895-904
  • George AM, Meyers NL, Hickling RI. Clinical trial: renzapride therapy for constipation-predominant irritable bowel syndrome – multicentre, randomized, placebo-controlled, double-blind study in primary healthcare setting. Aliment Pharmacol Ther 2008;27(9):830-7
  • Spiller RC, Meyers NL, Hickling RI. Identification of patients with non-d, non-C irritable bowel syndrome and treatment with renzapride: an exploratory, multicenter, randomized, double-blind, placebo-controlled clinical trial. Dig Dis Sci 2008;53(12):3191-200
  • Meyers NL, Hickling RI. Pharmacology and metabolism of renzapride: a novel therapeutic agent for the potential treatment of irritable bowel syndrome. Drugs R D 2008;9(1):37-63
  • Lembo AJ, Cremonini F, Meyers N, Hickling R. Clinical trial: renzapride treatment of women with irritable bowel syndrome and constipation – a double-blind, randomized, placebo-controlled, study. Aliment Pharmacol Ther 2010;31(9):979-90
  • Farber L, Haus U, Spath M, Drechsler S. Physiology and pathophysiology of the 5-HT3 receptor. Scand J Rheumatol Suppl 2004;119:2-8
  • Hirata T, Funatsu T, Keto Y, Pharmacological profile of ramosetron, a novel therapeutic agent for IBS. Inflammopharmacology 2007;15(1):5-9
  • Matsueda K, Harasawa S, Hongo M, 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 2008;43(10):1202-11
  • Matsueda K, Harasawa S, Hongo M, 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 2008;77(3-4):225-35
  • Briejer MR, Akkermans LM, Schuurkes JA. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev 1995;47(4):631-51
  • Grider JR, Foxx-Orenstein AE, Jin JG. 5-Hydroxytryptamine4 receptor agonists initiate the peristaltic reflex in human, rat, and guinea pig intestine. Gastroenterology 1998;115(2):370-80
  • Jin JG, Foxx-Orenstein AE, Grider JR. Propulsion in guinea pig colon induced by 5-hydroxytryptamine (HT) via 5-HT4 and 5-HT3 receptors. J Pharmacol Exp Ther 1999;288(1):93-7
  • Briejer MR, Prins NH, Schuurkes JA. Effects of the enterokinetic prucalopride (R093877) on colonic motility in fasted dogs. Neurogastroenterol Motil 2001;13(5):465-72
  • Bassotti G, Villanacci V. Slow transit constipation: a functional disorder becomes an enteric neuropathy. World J Gastroenterol 2006;12(29):4609-13
  • Coremans G, Kerstens R, De Pauw M, Stevens M. 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 2003;67(1-2):82-9
  • Emmanuel AV, Roy AJ, Nicholls TJ, Kamm MA. Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther 2002;16(7):1347-56
  • Sloots CE, Poen AC, Kerstens R, Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation. Aliment Pharmacol Ther 2002;16(4):759-67
  • Camilleri M, Beyens G, Kerstens R, Safety assessment of prucalopride in elderly patients with constipation: a double-blind, placebo-controlled study. Neurogastroenterol Motil 2009;21(12):1256-e117
  • Mine Y, Yoshikawa T, Oku S, Comparison of effect of mosapride citrate and existing 5-HT4 receptor agonists on gastrointestinal motility in vivo and in vitro. J Pharmacol Exp Ther 1997;283(3):1000-8
  • Inui A, Yoshikawa T, Nagai R, Effects of mosapride citrate, a 5-HT4 receptor agonist, on colonic motility in conscious guinea pigs. Jpn J Pharmacol 2002;90(4):313-20
  • Kim HS, Choi EJ, Park H. The effect of mosapride citrate on proximal and distal colonic motor function in the guinea-pig in vitro. Neurogastroenterol Motil 2008;20(2):169-76
  • Shimatani H, Kojima Y, Kadowaki M, A 5-HT4 agonist mosapride enhances rectorectal and rectoanal reflexes in guinea pigs. Am J Physiol Gastrointest Liver Physiol 2003;285(2):G389-95
  • Itoh H, Nagano T, Takeyama M. Effects of mosapride citrate on human plasma levels of motilin, gastrin, somatostatin, and secretin. Biol Pharm Bull 2001;24(9):1072-5
  • Carlsson L, Amos GJ, Andersson B, Electrophysiological characterization of the prokinetic agents cisapride and mosapride in vivo and in vitro: implications for proarrhythmic potential? J Pharmacol Exp Ther 1997;282(1):220-7
  • Kii Y, Ito T. Effects of 5-HT4-receptor agonists, cisapride, mosapride citrate, and zacopride, on cardiac action potentials in guinea pig isolated papillary muscles. J Cardiovasc Pharmacol 1997;29(5):670-5
  • Katoh T, Saitoh H, Ohno N, Drug interaction between mosapride and erythromycin without electrocardiographic changes. Jpn Heart J 2003;44(2):225-34
  • Ohki R, Takahashi M, Mizuno O, Torsades de pointes ventricular tachycardia induced by mosapride and flecainide in the presence of hypokalemia. Pacing Clin Electrophysiol 2001;24(1):119-21
  • Odaka T, Suzuki T, Seza A, Serotonin 5- HT4 receptor agonist (mosapride citrate). Nippon Rinsho 2006;64(8):1491-4
  • Mikami T, Ochi Y, Suzuki K, 5-Amino-6-chloro-N-[(1-isobutylpiperidin-4-yl)methyl]-2-methylimidazo[1,2-alpha]pyridine-8-carboxamide (CJ-033,466), a novel and selective 5-hydroxytryptamine4 receptor partial agonist: pharmacological profile in vitro and gastroprokinetic effect in conscious dogs. J Pharmacol Exp Ther 2008;325(1):190-9
  • Beattie DT, Smith JA, Marquess D, The 5-HT4 receptor agonist, tegaserod, is a potent 5-HT2B receptor antagonist in vitro and in vivo. Br J Pharmacol 2004;143(5):549-60
  • Prins NH, Briejer MR, Van Bergen PJ, Evidence for 5-HT7 receptors mediating relaxation of human colonic circular smooth muscle. Br J Pharmacol 1999;128(4):849-52
  • Tam FS, Hillier K, Bunce KT, Grossman C. Differences in response to 5-HT4 receptor agonists and antagonists of the 5-HT4-like receptor in human colon circular smooth muscle. Br J Pharmacol 1995;115(1):172-6
  • Bertrand PP, Kunze WA, Furness JB, Bornstein JC. The terminals of myenteric intrinsic primary afferent neurons of the guinea-pig ileum are excited by 5-hydroxytryptamine acting at 5-hydroxytryptamine-3 receptors. Neuroscience 2000;101(2):459-69
  • Mikami T, Komada T, Sugimoto H, In vitro and in vivo pharmacological characterization of PF-01354082, a novel partial agonist selective for the 5-HT(4) receptor. Eur J Pharmacol 2009;609(1-3):5-12
  • Smith JA, Beattie DT, Marquess D, The in vitro pharmacological profile of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol 2008;378(1):125-37
  • Beattie DT, Armstrong SR, Shaw JP, The in vivo gastrointestinal activity of TD-5108, a selective 5-HT(4) receptor agonist with high intrinsic activity. Naunyn Schmiedebergs Arch Pharmacol 2008;378(1):139-47
  • Manini ML, Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation. Neurogastroenterol Motil 2010;22(1):42-9, e7-8
  • Camilleri M, Pharmacodynamic effects of a novel prokinetic 5-HT receptor agonist, ATI-7505, in humans. Neurogastroenterol Motil 2007;19(1):30-8
  • Tamaoki S, Pharmacological properties of 3-amino-5,6,7,8- tetrahydro-2-[4-[4-(quinolin-2-yl)piperazin-1-yl]butyl]qui nazolin-4(3H)-one (TZB-30878), a novel therapeutic agent for diarrhea-predominant irritable bowel syndrome (IBS) and its effects on an experimental IBS model. J Pharmacol Exp Ther 2007;322(3):1315-23
  • Chey WD, Cash BD. Cilansetron: a new serotonergic agent for the irritable bowel syndrome with diarrhoea. Expert Opin Investig Drugs 2005;14(2):185-93
  • Brown P, Jackson J, Shi Z-C. LX1031: a new approach for managing irritable bowel syndrome (IBS). Gastroenterology 2009;136(Suppl 1):237
  • Drossman DA, Danilewitz M, Naesdal J, Randomized, double-blind, placebo-controlled trial of the 5-HT1A receptor antagonist AZD7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome. Am J Gastroenterol 2008;103(10):2562-9
  • Gorard DA, Libby GW, Farthing MJ. Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther 1994;8(2):159-66
  • Tabas G, Beaves M, Wang J, Paroxetine to treat irritable bowel syndrome not responding to high-fiber diet: a double-blind, placebo-controlled trial. Am J Gastroenterol 2004;99(5):914-20
  • Kuiken SD, Tytgat GN, Boeckxstaens GE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo-controlled study. Clin Gastroenterol Hepatol 2003;1(3):219-28
  • Tack J, Broekaert D, Corsetti M, Influence of acute serotonin reuptake inhibition on colonic sensorimotor function in man. Aliment Pharmacol Ther 2006;23(2):265-74
  • Tack J, Broekaert D, Fischler B, A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut 2006;55(8):1095-103
  • Chial HJ, Camilleri M, Ferber I, Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans. Clin Gastroenterol Hepatol 2003;1(3):211-18
  • Drossman DA, Toner BB, Whitehead WE, Cognitive-behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology 2003;125(1):19-31
  • Abdul-Baki H, El H II, Elzahabi L, A randomized controlled trial of imipramine in patients with irritable bowel syndrome. World J Gastroenterol 2009;15(29):3636-42
  • Kim DY, Camilleri M. Serotonin: a mediator of the brain-gut connection. Am J Gastroenterol 2000;95(10):2698-709
  • Bharucha AE, Camilleri M, Zinsmeister AR, Hanson RB. Adrenergic modulation of human colonic motor and sensory function. Am J Physiol 1997;273(5 Pt 1):G997-1006
  • Chang EB, Bergenstal RM, Field M. Diarrhea in streptozocin-treated rats. Loss of adrenergic regulation of intestinal fluid and electrolyte transport. J Clin Invest 1985;75(5):1666-70
  • Viramontes BE, Malcolm A, Camilleri M, Effects of an alpha(2)-adrenergic agonist on gastrointestinal transit, colonic motility, and sensation in humans. Am J Physiol Gastrointest Liver Physiol 2001;281(6):G1468-76
  • Camilleri M, Kim DY, McKinzie S, A randomized, controlled exploratory study of clonidine in diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2003;1(2):111-21
  • Cellek S, Thangiah R, Bassil AK, Demonstration of functional neuronal beta3-adrenoceptors within the enteric nervous system. Gastroenterology 2007;133(1):175-83
  • Manara L, Croci T, Aureggi G, Functional assessment of beta adrenoceptor subtypes in human colonic circular and longitudinal (taenia coli) smooth muscle. Gut 2000;47(3):337-42
  • Grudell AB, Camilleri M, Jensen KL, Dose-response effect of a beta3-adrenergic receptor agonist, solabegron, on gastrointestinal transit, bowel function, and somatostatin levels in health. Am J Physiol Gastrointest Liver Physiol 2008;294(5):G1114-19
  • Drossman DA, Leserman J, Nachman G, Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med 1990;113(11):828-33
  • Saito K, Kasai T, Nagura Y, Corticotropin-releasing hormone receptor 1 antagonist blocks brain-gut activation induced by colonic distention in rats. Gastroenterology 2005;129(5):1533-43
  • Baigent SM, Lowry PJ. mRNA expression profiles for corticotrophin-releasing factor (CRF), urocortin, CRF receptors and CRF-binding protein in peripheral rat tissues. J Mol Endocrinol 2000;25(1):43-52
  • Fukudo S, Nomura T, Muranaka M, Taguchi F. Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study. J Clin Gastroenterol 1993;17(2):133-41
  • Lenz HJ, Raedler A, Greten H, Stress-induced gastrointestinal secretory and motor responses in rats are mediated by endogenous corticotropin-releasing factor. Gastroenterology 1988;95(6):1510-17
  • Sagami Y, Shimada Y, Tayama J, Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome. Gut 2004;53(7):958-64
  • Tayama J, Sagami Y, Shimada Y, Effect of alpha-helical CRH on quantitative electroencephalogram in patients with irritable bowel syndrome. Neurogastroenterol Motil 2007;19(6):471-83
  • Lembo T, Plourde V, Shui Z, Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans. Neurogastroenterol Motil 1996;8(1):9-18
  • Fukudo S, Nomura T, Hongo M. Impact of corticotropin-releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut 1998;42(6):845-9
  • Tache Y, Martinez V, Million M, Maillot C. Role of corticotropin releasing factor receptor subtype 1 in stress-related functional colonic alterations: implications in irritable bowel syndrome. Eur J Surg Suppl 2002;(587):16-22
  • Habib KE, Weld KP, Rice KC, Oral administration of a corticotropin-releasing hormone receptor antagonist significantly attenuates behavioral, neuroendocrine, and autonomic responses to stress in primates. Proc Natl Acad Sci USA 2000;97(11):6079-84
  • Million M, Grigoriadis DE, Sullivan S, A novel water-soluble selective CRF1 receptor antagonist, NBI 35965, blunts stress-induced visceral hyperalgesia and colonic motor function in rats. Brain Res 2003;985(1):32-42
  • Sweetser S, Camilleri M, Linker Nord SJ, Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome? Am J Physiol Gastrointest Liver Physiol 2009;296(6):G1299-306
  • Niederau C, Faber S, Karaus M. Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome. Gastroenterology 1992;102(6):1889-98
  • Sabate JM, Gorbatchef C, Flourie B, Cholecystokinin octapeptide increases rectal sensitivity to pain in healthy subjects. Neurogastroenterol Motil 2002;14(6):689-95
  • Van Der Veek PP, Biemond I, Masclee AA. Proximal and distal gut hormone secretion in irritable bowel syndrome. Scand J Gastroenterol 2006;41(2):170-7
  • Kellow JE, Miller LJ, Phillips SF, Altered sensitivity of the gallbladder to cholecystokinin octapeptide in irritable bowel syndrome. Am J Physiol 1987;253(5 Pt 1):G650-5
  • Kellow JE, Phillips SF, Miller LJ, Zinsmeister AR. Dysmotility of the small intestine in irritable bowel syndrome. Gut 1988;29(9):1236-43
  • Chey WY, Jin HO, Lee MH, Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001;96(5):1499-506
  • Scarpignato C, Pelosini I. Management of irritable bowel syndrome: novel approaches to the pharmacology of gut motility. Can J Gastroenterol 1999;13(Suppl A):50A-65A
  • Cremonini F, Camilleri M, McKinzie S, Effect of CCK-1 antagonist, dexloxiglumide, in female patients with irritable bowel syndrome: a pharmacodynamic and pharmacogenomic study. Am J Gastroenterol 2005;100(3):652-63
  • Varga G. Dexloxiglumide Rotta Research Lab. Curr Opin Investig Drugs 2002;3(4):621-6
  • Coulie B, Szarka LA, Camilleri M, Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans. Gastroenterology 2000;119(1):41-50
  • Parkman HP, Rao SS, Reynolds JC, Neurotrophin-3 improves functional constipation. Am J Gastroenterol 2003;98(6):1338-47
  • Nyhlin H, Ford MJ, Eastwood J, Non-alimentary aspects of the irritable bowel syndrome. J Psychosom Res 1993;37(2):155-62
  • Kumar D, Thompson PD, Wingate DL, Abnormal REM sleep in the irritable bowel syndrome. Gastroenterology 1992;103(1):12-17
  • Jarrett M, Heitkemper M, Cain KC, Sleep disturbance influences gastrointestinal symptoms in women with irritable bowel syndrome. Dig Dis Sci 2000;45(5):952-9
  • Cardinali DP, Gvozdenovich E, Kaplan MR, A double blind-placebo controlled study on melatonin efficacy to reduce anxiolytic benzodiazepine use in the elderly. Neuro Endocrinol Lett 2002;23(1):55-60
  • Bubenik GA, Dhanvantari S. Influence of serotonin and melatonin on some parameters of gastrointestinal activity. J Pineal Res 1989;7(4):333-44
  • Bubenik GA. Gastrointestinal melatonin: localization, function, and clinical relevance. Dig Dis Sci 2002;47(10):2336-48
  • Bubenik GA, Pang SF. The role of serotonin and melatonin in gastrointestinal physiology: ontogeny, regulation of food intake, and mutual serotonin-melatonin feedback. J Pineal Res 1994;16(2):91-9
  • Roberts-Thomson IC, Knight RE, Kennaway DJ, Pannall PR. Circadian rhythms in patients with abdominal pain syndromes. Aust NZ J Med 1988;18(4):569-74
  • Stepien A, Moskwa-Fortuna A, Wisniewska-Jarosinska M, Melatonin secretion and metabolism in patients with irritable bowel syndrome. Pol Merkur Lekarski 2009;26(155):440-3
  • Song GH, Leng PH, Gwee KA, Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut 2005;54(10):1402-7
  • Lu WZ, Song GH, Gwee KA, Ho KY. The effects of melatonin on colonic transit time in normal controls and IBS patients. Dig Dis Sci 2009;54(5):1087-93
  • Saha L, Malhotra S, Rana S, A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41(1):29-32
  • Komarov FI, Raikhlin NT, Rapoport SI, Irritated bowel syndrome: clinicomorphological aspects of treatment with melaxen. Klin Med (Mosk) 2006;84(11):30-6
  • Hwang JH, Yaksh TL. Effect of subarachnoid gabapentin on tactile-evoked allodynia in a surgically induced neuropathic pain model in the rat. Reg Anesth 1997;22(3):249-56
  • Gottrup H, Juhl G, Kristensen AD, Chronic oral gabapentin reduces elements of central sensitization in human experimental hyperalgesia. Anesthesiology 2004;101(6):1400-8
  • Lee KJ, Kim JH, Cho SW. Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2005;22(10):981-8
  • Horvath EJ, Horvath K, Hamori T, Anxiolytic 2,3-benzodiazepines, their specific binding to the basal ganglia. Prog Neurobiol 2000;60(4):309-42
  • Leventer SM, Raudibaugh K, Frissora CL, Clinical trial: dextofisopam in the treatment of patients with diarrhoea-predominant or alternating irritable bowel syndrome. Aliment Pharmacol Ther 2008;27(2):197-206
  • Eutamene H, Bradesi S, Larauche M, Guanylate cyclase C-mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil 2010;22(3):312-e84
  • Johnston JM, Kurtz CB, Drossman DA, Pilot study on the effect of linaclotide in patients with chronic constipation. Am J Gastroenterol 2009;104(1):125-32
  • Andresen V, Camilleri M, Busciglio IA, Effect of 5 days linaclotide on transit and bowel function in females with constipation-predominant irritable bowel syndrome. Gastroenterology 2007;133(3):761-8
  • Holzer P. Opioids and opioid receptors in the enteric nervous system: from a problem in opioid analgesia to a possible new prokinetic therapy in humans. Neurosci Lett 2004;361(1-3):192-5
  • De Schepper HU, Cremonini F, Park MI, Camilleri M. Opioids and the gut: pharmacology and current clinical experience. Neurogastroenterol Motil 2004;16(4):383-94
  • Kurz A, Sessler DI. Opioid-induced bowel dysfunction: pathophysiology and potential new therapies. Drugs 2003;63(7):649-71
  • Delvaux M, Louvel D, Lagier E, The kappa agonist fedotozine relieves hypersensitivity to colonic distention in patients with irritable bowel syndrome. Gastroenterology 1999;116(1):38-45
  • Walker J, Catheline G, Guilbaud G, Kayser V. Lack of cross-tolerance between the antinociceptive effects of systemic morphine and asimadoline, a peripherally-selective kappa-opioid agonist, in CCI-neuropathic rats. Pain 1999;83(3):509-16
  • Burton MB, Gebhart GF. Effects of kappa-opioid receptor agonists on responses to colorectal distension in rats with and without acute colonic inflammation. J Pharmacol Exp Ther 1998;285(2):707-15
  • Delvaux M, Beck A, Jacob J, Effect of asimadoline, a kappa opioid agonist, on pain induced by colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther 2004;20(2):237-46
  • Szarka LA, Camilleri M, Burton D, Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome. Clin Gastroenterol Hepatol 2007;5(11):1268-75
  • Mangel AW, Bornstein JD, Hamm LR, Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther 2008;28(2):239-49
  • Kreek MJ, Schaefer RA, Hahn EF, Fishman J. Naloxone, a specific opioid antagonist, reverses chronic idiopathic constipation. Lancet 1983;1(8319):261-2
  • Sykes NP. Oral naloxone in opioid-associated constipation. Lancet 1991;337(8755):1475
  • Hawkes ND, Richardson C, Evans BK, Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine. Aliment Pharmacol Ther 2001;15(5):625-30
  • Hawkes ND, Rhodes J, Evans BK, Naloxone treatment for irritable bowel syndrome – a randomized controlled trial with an oral formulation. Aliment Pharmacol Ther 2002;16(9):1649-54
  • Shen KF, Crain SM. Ultra-low doses of naltrexone or etorphine increase morphine's antinociceptive potency and attenuate tolerance/dependence in mice. Brain Res 1997;757(2):176-90
  • Shen KF, Crain SM. Dual opioid modulation of the action potential duration of mouse dorsal root ganglion neurons in culture. Brain Res 1989;491(2):227-42
  • Crain SM, Shen KF. Opioids can evoke direct receptor-mediated excitatory effects on sensory neurons. Trends Pharmacol Sci 1990;11(2):77-81
  • Fan SF, Shen KF, Crain SM. Opioids at low concentration decrease openings of K+ channels in sensory ganglion neurons. Brain Res 1991;558(1):166-70
  • Xu H, Smolens I, Gintzler AR. Opioids can enhance and inhibit the electrically evoked release of methionine-enkephalin. Brain Res 1989;504(1):36-42
  • Kariv R, Tiomny E, Grenshpon R, Low-dose naltreoxone for the treatment of irritable bowel syndrome: a pilot study. Dig Dis Sci 2006;51(12):2128-33
  • La JH, Kim TW, Sung TS, Increase in neurokinin-1 receptor-mediated colonic motor response in a rat model of irritable bowel syndrome. World J Gastroenterol 2005;11(2):237-41
  • Lecci A, Capriati A, Maggi CA. Tachykinin NK2 receptor antagonists for the treatment of irritable bowel syndrome. Br J Pharmacol 2004;141(8):1249-63
  • Okano S, Nagaya H, Ikeura Y, Effects of TAK-637, a novel neurokinin-1 receptor antagonist, on colonic function in vivo. J Pharmacol Exp Ther 2001;298(2):559-64
  • Okano S, Ikeura Y, Inatomi N. Effects of tachykinin NK1 receptor antagonists on the viscerosensory response caused by colorectal distention in rabbits. J Pharmacol Exp Ther 2002;300(3):925-31
  • Lee O, Munakata J, Naliboff B, A double-blind parallel group pilot study of the effects of CJ-11974 and placebo on perceptual and emotional responses rectosigmoid distensions in IBS patients. Gastroenterology 2000;118:A846
  • Toulouse M, Coelho AM, Fioramonti J, Role of tachykinin NK2 receptors in normal and altered rectal sensitivity in rats. Br J Pharmacol 2000;129(1):193-9
  • Eutamene H, Theodorou V, Fioramonti J, Bueno L. Rectal distention-induced colonic net water secretion in rats involves tachykinins, capsaicin sensory, and vagus nerves. Gastroenterology 1997;112(5):1595-602
  • Mule F, D'Angelo S, Tabacchi G, Serio R. Involvement of tachykinin NK2 receptors in the modulation of spontaneous motility in rat proximal colon. Neurogastroenterol Motil 2000;12(5):459-66
  • Lordal M, Navalesi G, Theodorsson E, A novel tachykinin NK2 receptor antagonist prevents motility-stimulating effects of neurokinin A in small intestine. Br J Pharmacol 2001;134(1):215-23
  • Tough IR, Lewis CA, Fozard J, Cox HM. Dual and selective antagonism of neurokinin NK(1) and NK(2) receptor-mediated responses in human colon mucosa. Naunyn Schmiedebergs Arch Pharmacol 2003;367(2):104-8
  • Onori L, Aggio A, Taddei G, Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon. Am J Physiol Gastrointest Liver Physiol 2003;285(2):G325-31
  • Kamp EH, Beck DR, Gebhart GF. Combinations of neurokinin receptor antagonists reduce visceral hyperalgesia. J Pharmacol Exp Ther 2001;299(1):105-13
  • Fioramonti J, Gaultier E, Toulouse M, Intestinal anti-nociceptive behaviour of NK3 receptor antagonism in conscious rats: evidence to support a peripheral mechanism of action. Neurogastroenterol Motil 2003;15(4):363-9
  • Houghton LA, Cremonini F, Camilleri M, Effect of the NK(3) receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. Neurogastroenterol Motil 2007;19(9):732-43

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