• 1
    Johanson JF, Kralstein J. Chronic constipation: a survey of the patient perspective. Aliment Pharmacol Ther 2007; 25: 599608.
  • 2
    Dennison C, Prasad M, Lloyd A, Bhattacharyya SK, Dhawan R, Coyne K. The health-related quality of life and economic burden of constipation. Pharmacoeconomics 2005; 23: 46176.
  • 3
    Stewart WF, Liberman JN, Sandler RS, et al. Epidemiology of constipation (EPOC) study in the United States: relation of clinical subtypes to sociodemographic features. Am J Gastroenterol 1999; 94: 353040.
    Direct Link:
  • 4
    Higgins PD, Johanson JF. Epidemiology of constipation in North America: a systematic review. Am J Gastroenterol 2004; 99: 7509.
    Direct Link:
  • 5
    Wald A, Kamm M, Mueller-Lissner S, Scarpignato C, Marx W, Schuijt C. The BI Omnibus study: an international survey of community prevalence of constipation and laxative use in adults. Gastroenterology 2006; 130: 508.
  • 6
    Wald A, Scarpignato C, Kamm MA, et al. The burden of constipation on quality of life: results of a multinational survey. Aliment Pharmacol Ther 2007; 26: 22736.
  • 7
    Glia A, Lindberg G. Quality of life in patients with different types of functional constipation. Scand J Gastroenterol 1997; 32: 10839.
  • 8
    Irvine EJ, Ferrazzi S, Pare P, Thompson WG, Rance L. Health-related quality of life in functional GI disorders: focus on constipation and resource utilization. Am J Gastroenterol 2002; 97: 198693.
    Direct Link:
  • 9
    Mason HJ, Serrano-Ikkos E, Kamm MA. Psychological morbidity in women with idiopathic constipation. Am J Gastroenterol 2000; 95: 28527.
    Direct Link:
  • 10
    Wald A. Chronic constipation: advances in management. Neurogastroenterol Motil 2007; 19: 410.
  • 11
    Yost KJ, Haan MN, Levine RA, Gold EB. Comparing SF-36 scores across three groups of women with different health profiles. Qual Life Res 2005; 14: 125161.
  • 12
    Johanson JF. Review of the treatment options for chronic constipation. Med Gen Med 2007; 9: 25.
  • 13
    Peppas G, Alexiou VG, Mourtzoukou E, Falagas ME. Epidemiology of constipation in Europe and Oceania: a systematic review. BMC Gastroenterol 2008; 8: 5.
  • 14
    Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology 2006; 130: 148091.
  • 15
    Ramkumar D, Rao SS. Efficacy and safety of traditional medical therapies for chronic constipation: systematic review. Am J Gastroenterol 2005; 100: 93671.
    Direct Link:
  • 16
    Johnson DA. Treating chronic constipation : How should we interpret the recommendations? Clin Drug Investig 2006; 26: 54757.
  • 17
    Bassotti G, Villanacci V. Slow transit constipation: a functional disorder becomes an enteric neuropathy. World J Gastroenterol 2006; 12: 460913.
  • 18
    Krishnamurthy S, Schuffler MD, Rohrmann CA, Pope CE II. Severe idiopathic constipation is associated with a distinctive abnormality of the colonic myenteric plexus. Gastroenterology 1985; 88: 2634.
  • 19
    Briejer MR, Akkermans LM, Schuurkes JA. Gastrointestinal prokinetic benzamides: the pharmacology underlying stimulation of motility. Pharmacol Rev 1995; 47: 63151.
  • 20
    Briejer MR, Schuurkes JA. 5-HT3 and 5-HT4 receptors and cholinergic and tachykininergic neurotransmission in the guinea-pig proximal colon. Eur J Pharmacol 1996; 308: 17380.
  • 21
    Briejer MR, Schuurkes JA, Sarna SK. Idiopathic constipation: too few stools and too little knowledge. Trends Pharmacol Sci 1999; 20: 13.
  • 22
    Tonini M. 5-Hydroxytryptamine effects in the gut: the 3, 4, and 7 receptors. Neurogastroenterol Motil 2005; 17: 63742.
  • 23
    Tonini M, De Giorgio R, Spelta V, et al. 5-HT4 receptors contribute to the motor stimulating effect of levosulpiride in the guinea-pig gastrointestinal tract. Dig Liver Dis 2003; 35: 24450.
  • 24
    Busti AJ, Murillo JRJ, Cryer B. Tegaserod-induced myocardial infarction: case report and hypothesis. Pharmacotherapy 2004; 24: 52631.
  • 25
    Potet F, Bouyssou T, Escande D, Baro I. Gastrointestinal prokinetic drugs have different affinity for the human cardiac human ether-a-gogo K+ channel. J Pharmacol Exp Ther 2001; 299: 100712.
  • 26
    Tonini M, De Ponti F, Di Nucci A, Crema F. Review article: cardiac adverse effects of gastrointestinal prokinetics. Aliment Pharmacol Ther 1999; 13: 158591.
  • 27
    Tonini M, Pace F. Drugs acting on serotonin receptors for the treatment of functional GI disorders. Dig Dis 2006; 24: 5969.
  • 28
    De Maeyer JH, Lefebvre RA, Schuurkes JA. 5-HT4 receptor agonists: similar but not the same. Neurogastroenterol Motil 2008; 20: 99112.
  • 29
    Van de Velde V, Ausma J, Vandeplassche L. Pharmacokinetics of prucalopride (Resolor®) in man. Gut 2008; 57(Suppl. II): A282.
  • 30
    Bouras EP, Camilleri M, Burton DD, McKinzie S. Selective stimulation of colonic transit by the benzofuran 5HT4 agonist, prucalopride, in healthy humans. Gut 1999; 44: 6826.
  • 31
    Bouras EP, Camilleri M, Burton DD, Thomforde G, McKinzie S, Zinsmeister AR. Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder. Gastroenterology 2001; 120: 35460.
  • 32
    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: 829.
  • 33
    Emmanuel AV, Kamm MA, Roy AJ, Antonelli K. Effect of a novel prokinetic drug, R093877, on gastrointestinal transit in healthy volunteers. Gut 1998; 42: 5116.
  • 34
    Emmanuel AV, Roy AJ, Nicholls TJ, Kamm MA. Prucalopride, a systemic enterokinetic, for the treatment of constipation. Aliment Pharmacol Ther 2002; 16: 134756.
  • 35
    Frank L, Kleinman L, Farup C, Taylor L, Miner P Jr. Psychometric validation of a constipation symptom assessment questionnaire. Scand J Gastroenterol 1999; 34: 8707.
  • 36
    Marquis P, De La Loge C, Dubois D, McDermott A, Chassany O. Development and validation of the Patient Assessment of Constipation Quality of Life questionnaire. Scand J Gastroenterol 2005; 40: 54051.
  • 37
    Ware JE, Kosinski M, Keller SK. SF-36® Physical and Mental Health Summary Scales: A User’s Manual. Boston, MA: The Health Institute, 1994.
  • 38
    Camilleri M, Kerstens R, Rykx A, Vandeplassche L. A placebo-controlled trial of prucalopride for severe chronic constipation. N Engl J Med 2008; 358: 234454.
  • 39
    Food and Drug Administration Center for Drug Evaluation and Research. Summary Minutes of the July 14, 2004 meeting of the Gastrointestinal Drugs Advisory Committee. New drug application 21-200/S-005, Zelnorm® (tegaserod maleate) Tablets, Novartis Pharmaceuticals Corp. “for the proposed indication of the treatment of patients with chronic constipation and relief of associated symptoms of straining, hard or lumpy stools and infrequent defecation”; cited 1 September 2008. Available at:, 2004.
  • 40
    Johanson JF, Wald A, Tougas G, et al. Effect of tegaserod in chronic constipation: a randomized, double-blind, controlled trial. Clin Gastroenterol Hepatol 2004; 2: 796805.
  • 41
    Johanson JF, Morton D, Geenen J, Ueno R. 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 2008; 103: 1707.
    Direct Link:
  • 42
    Charach G, Greenstein A, Rabinovich P, Groskopf I, Weintraub M. Alleviating constipation in the elderly improves lower urinary tract symptoms. Gerontology 2001; 47: 726.
  • 43
    Nyam DC, Pemberton JH, Ilstrup DM, Rath DM. Long-term results of surgery for chronic constipation. Dis Colon Rectum 1997; 40: 2739.
  • 44
    Reilly MC, Barghout V, McBurney CR, Niecko TE. Effect of tegaserod on work and daily activity in irritable bowel syndrome with constipation. Aliment Pharmacol Ther 2005; 22: 37380.
  • 45
    Tack J, Muller-Lissner S, Bytzer P, et al. A randomised controlled trial assessing the efficacy and safety of repeated tegaserod therapy in women with irritable bowel syndrome with constipation. Gut 2005; 54: 170713.
  • 46
    Briejer MR, Bosmans JP, Van Daele P, et al. The in vitro pharmacological profile of prucalopride, a novel enterokinetic compound. Eur J Pharmacol 2001; 423: 7183.
  • 47
    Boyce MJ, Carrey W, Mannaert EJ, Mertens A, Ausma J. Cardiovascular safety of prucalopride (Resolor) in healthy subjects: results from a randomized, double-blind, placebo-controlled, cross-over trial. Gastrointest Endosc 2008; 67: T1418.
  • 48
    Krogh K, Jensen MB, Gandrup P, et al. Efficacy and tolerability of prucalopride in patients with constipation due to spinal cord injury. Scand J Gastroenterol 2002; 37: 4316.
  • 49
    Sloots CE, Poen AC, Kerstens R, et al. Effects of prucalopride on colonic transit, anorectal function and bowel habits in patients with chronic constipation. Aliment Pharmacol Ther 2002; 16: 75967.
  • 50
    Committee for Proprietary Medicinal Products. Points to Consider: The Assessment of the Potential for QT Interval Prolongation by Non-cardiovascular Medicinal Products. London, 17 December 1997, CPMP/986/96, 1997.