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Prokinetic agents for lower gastrointestinal motility disorders

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Diseases of the Colon & Rectum

Abstract

Prokinetic agents are currently being investigated as potential therapies for motility disorders of the lower gastrointestinal tract. Cholinergic agonists such as bethanechol are known to improve postoperative ileus but are limited because of side effects. Dopamine antagonists such as domperidone appear to have maximal prokinetic effect in the proximal gastrointestinal tract and are effective for such conditions as gastroparesis and gastroesophageal reflux, but they appear to have little physiologic effect in the colon or in colonic motility disorders. Naloxone, an opioid antagonist, appears to hold promise in patients with irritable bowel syndrome, small intestinal pseudo-obstruction, and constipation. Erythromycin exerts its prokinetic effect by acting as a motilin agonist; it has been used in the treatment of diabetic gastroparesis and appears to improve symptoms of colonic pseudoobstruction and postoperative ileus. Metoclopramide, a combined cholinergic agonist and dopamine antagonist, is currently used exclusively for proximal motility dysfunction. Cisapride appears to hold the most promise for patients with colonie motility disorders. In patients with postoperative ileus, cisapride is associated with an increased return of bowel function compared with placebo. In patients with chronic constipation, cisapride increases stool frequency and decreases laxative abuse in both adults and children. Hopefully, as an understanding of gastrointestinal motility increases, effective prokinetic agents will be developed that will improve symptoms of patients with large bowel motility disorders and may also help to predict those patients who benefit from surgical management for constipation.

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References

  1. Bright-Asare P, El Bassoussi M. Cimetidine, metoclopramide or placebo in the treatment of symptomatic gastroesophageal reflux. J Clin Gastroenterol 1980;25:750–5.

    Google Scholar 

  2. Muller-Lissner SA, Fraels C, Hartl A. Cisapride offsets dopamine-induced slowing of fasting gastric emptying. Dig Dis Sci 1986;31:807–10.

    Article  PubMed  Google Scholar 

  3. Bailey LD, Stewart WR, McCallum RW. New directions in the irritable bowel syndrome. Gastroenterol Clin North Am 1991;20:335–49.

    PubMed  Google Scholar 

  4. McCallum RW. Review of the current status of prokinetic agents in gastroenterology. Am J Gastroenterol 1985;80:1008–16.

    PubMed  Google Scholar 

  5. Reynolds JC. Prokinetic agents: a key in the future of gastroenterology. Gastroenterol Clin North Am 1989;18:437–57.

    PubMed  Google Scholar 

  6. Reynolds JC, Putnam PE. Prokinetic agents. Gastroenterol Clin North Am 1992;21:567–96.

    PubMed  Google Scholar 

  7. Gray H. Anatomy of the human body. Philadelphia: Lea and Febiger, 1973:1004–36.

    Google Scholar 

  8. Goligher J. Surgery of the anus, rectum and colon. London: Bailliere Tindall, 1984:1–47.

    Google Scholar 

  9. Telford ED, Stopford JS. The autonomic nerve supply of the distal colon: an anatomical and clinical study. BMJ 1934;1:572–4.

    Google Scholar 

  10. Labate JS. The anatomy of the superior hypogastric plexus-“pre-sacral nerve.” Surg Gynecol Obstet 1938;67:199–211.

    Google Scholar 

  11. Cooke HJ. Neurobiology of the intestinal mucosa. Gastroenterology 1986;90:1057–81.

    PubMed  Google Scholar 

  12. Christensen J. Motility of the colon. In: Johnson LR, ed. Physiology of the gastrointestinal tract. New York: Raven Press, 1981:445–71.

    Google Scholar 

  13. Longo WE, Ballantyne GH, Modlin IM. The colon, anorectum and spinal cord patient: a review of the functional alterations of the denervated hindgut. Dis Colon Rectum 1989;32:261–7.

    PubMed  Google Scholar 

  14. Grider JR, Malchlouf GM. Colonic peristaltic reflex: identification of vasoactive intestinal peptide as mediator of descending relaxation. Am J Physiol 1986;251(Gastrointest Liver Physiol 14):G40–5.

    PubMed  Google Scholar 

  15. Snape WJ Jr, Wright SH, Cohen S, Battle WM. The gastrocolonic response: evidence for a neural mechanism-neural versus hormonal mediation. Gastroenterology 1979;77:1235–40.

    PubMed  Google Scholar 

  16. Weisbrodt NW. Gastrointestinal motility. In: Guyton AC, Jacobson ED, Shanbour LL, eds. Gastrointestinal physiology. Baltimore: University Park Press, 1974.

    Google Scholar 

  17. Rennie JA, Christofides ND, Bloom SR, Johnson AG. Stimulation of human colonic activity by motilin. Gut 1979;20:916–26.

    Google Scholar 

  18. Zara GP, Thompson HH, Pilot MA, Ritchie HD. Effects of erythromycin on gastrointestinal tract motility. J Antimicrob Chemother 1985;16(Suppl A):175–9.

    PubMed  Google Scholar 

  19. Lundberg JM, Tatemoto K. Localization of peptide YY (PYY) in gastrointestinal endocrine cells and effects on intestinal blood flow and motility. Proc Natl Acad Sci USA 1982;79:4471–5.

    PubMed  Google Scholar 

  20. Kinoso VP, Meshkinpour H, Lorber SH, Gutirrez JG, Chey WY. Motor responses of the sigmoid colon and rectum to exogenous cholecystokinin and secretin. Gastroenterology 1973;65:438–44.

    PubMed  Google Scholar 

  21. Ryan JP, Bhojwani A. Colon transit in rats: effect of ovariectomy, sex steroid hormones and pregnancy. Am J Physiol 1986;251(Gastrointest Liver Physiol 14):G36–50.

    Google Scholar 

  22. Burks TF. Actions of drugs on gastrointestinal motility. In: Johnson LR, ed. Physiology of the gastrointestinal tract. Vol. 1. New York: Raven Press, 1987:723–43.

    Google Scholar 

  23. Hammer R, Giachetti A. Muscarinic receptors subtypes: Ml and M2. Biochemical and functional characterization. Life Sci 1982;31:2991–8.

    Article  PubMed  Google Scholar 

  24. Gillis RA, Dias Souza J, Hicks KA,et al. Inhibitory control of proximal colonie motility by the sympathetic nervous system. Am J Physiol 1987;253(Gastrointest Liver Physiol 16):G531–9.

    PubMed  Google Scholar 

  25. Snape WJ, Shiff S. Neurohumoral control of colonie motility in the rabbit. Am J Physiol 1983;245(Gastrointest Liver Physiol 8):G582–8.

    PubMed  Google Scholar 

  26. Cohen S, Green F. Force velocity characteristics of esophageal muscle: effect of acetylcholine and norepinephrine. Am J Physiol 1974;226:1250–5.

    PubMed  Google Scholar 

  27. Miller WN, Ganeshappa KP, Dodds WJ,et al. Effects of bethanechol on gastroesophageal reflux. Am J Dig Dis 1977;22:230–4.

    Article  PubMed  Google Scholar 

  28. Thanik DI, Chey WY, Shah AN,et al. Reflux esophagitis: effect of oral bethanechol on symptoms and endoscopic findings. Ann Intern Med 1980;93:805–8.

    PubMed  Google Scholar 

  29. McCallum RW, Fink SM, Lerner E,et al. Effects of metoclopramide and bethanechol on delayed gastric emptying present in gastroesophageal reflux patients. Gastroenterology 1983;84:1573.

    PubMed  Google Scholar 

  30. Furness JB, Costa M. A dynamic ileus, its pathogenesis and treatment. Med Biol 1974;52:82–9.

    PubMed  Google Scholar 

  31. Ruwart MJ, Klepper MS, Rush BD. Carbachol stimulation of gastrointestinal transit in the postoperative ileus rat. J Surg Res 1979;26:18–26.

    Article  PubMed  Google Scholar 

  32. Besancou JL, Laville C, Thominet M. Le metoclopramide et ses homoloques: introduction a leur etude biologique. C R Acad Sci 1964;258:4384–6.

    Google Scholar 

  33. Jacoby HI, Brodie DA. Gastrointestinal actions of metoclopramide: an experimental study. Gastroenterology 1967;52:676.

    PubMed  Google Scholar 

  34. Jenner P, Marsden CD. The substituted benzamides—a novel class of dopamine antagonists. Life Sci 1979;25:479–85.

    Article  PubMed  Google Scholar 

  35. Albibi R, McCallum RW. Metoclopramide: pharmacology and clinical application. Ann Intern Med 1983;98:86–95.

    PubMed  Google Scholar 

  36. Beani L, Bianchi C, Cremer C. Effects of metoclopramide on isolated guinea pig colon. 1. Peripheral sensitization to acetylcholine. Eur J Pharmacol 1970;12:220–31.

    Article  Google Scholar 

  37. Wallin L, Boesby S, Madsen T. Effect of metoclopramide on oesophageal peristalsis and gastroesophageal sphincter pressure. Scand J Gastroenterol 1979;14:923–7.

    PubMed  Google Scholar 

  38. Davidson ED, Hersh T, Ilaun C, Brooks WS. Use of metoclopramide in patients with delayed gastric emptying following gastric surgery. Am Surg 1977;43:40–4.

    PubMed  Google Scholar 

  39. James WB, Hume R. Action of metoclopramide on gastric emptying and small bowel transit time. Gut 1968;9:203–5.

    PubMed  Google Scholar 

  40. Battle WM, Snape WJ, Alavi A,et al. Colonic dysfunction in diabetes mellitus. Gastroenterology 1980;79:1217–21.

    PubMed  Google Scholar 

  41. Eisner M. Gastrointestinal effects of metoclopramide in man: in vitro experiments with human smooth muscle preparations. BMJ 1968;4:679–80.

    PubMed  Google Scholar 

  42. Fuchs B. Prevention of meal-induced heartburn and regurgitation with metoclopramide in patients with gastroesophageal reflux. Clin Ther 1982;5:179–85.

    PubMed  Google Scholar 

  43. McCallum RW, Fink SM, Winnan GR,et al. Metoclopramide in gastroesophageal reflux disease: rationale for its use and results of a double blind trial. Am J Gastroenterol 1984;79:165–72.

    PubMed  Google Scholar 

  44. Minami H, McCallum RW. The physiology and pathophysiology of gastric emptying in humans. Gastroenterology 1984;86:1592–610.

    PubMed  Google Scholar 

  45. Pinder RM, Brogden RN, Sawyer PR. Metoclopramide: a review of its pharmacological properties and clinical use. Drugs 1976;12:81–131.

    PubMed  Google Scholar 

  46. Davidson ED, Hersh T, Ilaun C,et al. Use of metoclopramide in patients with delayed gastric emptying following gastric surgery. Am Surg 1977;43:40–4.

    PubMed  Google Scholar 

  47. Lipton AB, Knauer CM. Pseudo-obstruction of the bowel: therapeutic trial of metoclopramide. Dig Dis 1977;22:263–5.

    Article  Google Scholar 

  48. Van Neuten JM, Reyntjens A, Schurkes JA. Gastrointestinal motility stimulating properties of the nonantidopaminergic and non-cholinergic compound R 41 619. Gastroenterol Clin Biol 1983;7:706.

    Google Scholar 

  49. Boeckxstaens GE, Pelckmans PA, Rampart M,et al. Pharmacological characterization of 5-hydroxytryptamine receptors in the canine terminal ileum and ileocolonic junction. J Pharmacol Exp Ther 1990;254:652–7.

    PubMed  Google Scholar 

  50. Koop H, Monnikes H, Koop I, Dionysius J, Schwarz C, Arnold R. Effect of the prokinetic drug cisapride on gastrointestinal hormone release. Scand J Gastroenterol 1986;21:907–13.

    PubMed  Google Scholar 

  51. Corazziari E, Scopinaro F, Bontempo G,et al. Effects of R-51619 on distal esophageal motor activity and gastric emptying. It al J Gastroenterol 1983;15:185–6.

    Google Scholar 

  52. Ceccatelli P, Janssens J, Van Trappen G,et al. Cisapride restores the decreased lower oesophageal sphincter pressure in reflux patients. Gut 1988;29:631–5.

    PubMed  Google Scholar 

  53. Janssens J, Ceccatelli P, Van Trappen G. Cisapride restores the decreased lower esophageal sphincter pressure in reflux patients. Digestion 1984;34:139.

    Google Scholar 

  54. Smout AJ, Bogaa JW, Grade AC, Thije OJ, Akkermans LM, Wittebol P. Effects of cisapride, a new gastrointestinal prokinetic substance on interdigestive and postprandial motor activity of the distal esophagus in man. Gut 1985;26:246–51.

    PubMed  Google Scholar 

  55. Muller-Lissner SA, Fraas C, Hartl A. Cisapride offsets dopamine-induced slowing of fasting gastric emptying. Dig Dis Sci 1986;31:807–10.

    Article  PubMed  Google Scholar 

  56. Stacher G, Sternringer H, Schneider C,et al. Effect of cisapride on jejunal motor activity in fasting healthy humans. Gastroenterology 1986;90:1210.

    PubMed  Google Scholar 

  57. Coremans G, Chaussade S, Janssen J,et al. Stimulation of propulsive motility patterns by cisapride in the upper gut of man. Dig Dis Sci 1985;30:765.

    Google Scholar 

  58. Den Hertog A, Adder JF. The effect of cisapride on smooth muscle cells of guinea pig taenia caeci. Eur J Pharmacol 1986;126:31–5.

    Article  PubMed  Google Scholar 

  59. Burleigh DE, Trout SJ. Evidence against an acetylcholine releasing action of cisapride in the human colon. Br J Clin Pharmacol 1985;20:475–8.

    PubMed  Google Scholar 

  60. Edwards CA, Holden S, Brown C, Read NW. Effect of cisapride on the gastrointestinal transit of a solid meal in normal human subjects. Gut 1987;28:13–6.

    PubMed  Google Scholar 

  61. McCallum RW, Petersen J, Caricle B,et al. Scintigraphic evaluation on colon transit in normal subjects: prokinetic effect of cisapride. Clin Res 1986;34:182A.

    Google Scholar 

  62. Krevsky B, Malmud L, Mauer A, Siegel J, Fisher RS. Effects of cisapride on colonie transit in man. Proceedings of the First International Cisapride Investigators' Meeting, p. 156, #43.

  63. Lederer E, Ellermann A, Schmidt H, Ernst V, Lux G. Effect of cisapride on sigmoid motility in healthy subjects and in diabetic enteropathy (DE) with constipation. Proceedings of the First International Cisapride Investigators' Meeting, p. 155, #41.

  64. Krevsky B, Malud LS, Maurer AH, Somers MB, Siegel JA, Fisher RS. The effect of oral cisapride on colonie transit. Aliment Pharmacol Ther 1987;1:293–304.

    PubMed  Google Scholar 

  65. Chey Wy, Lee KY, You CH. Effect of cisapride on colonic transit time in dogs and humans. Dig Dis Sci 1984;7:29.

    Google Scholar 

  66. Enck P, Arping HG, Engel S, Bielefeldt K, Erckenbrecht JF. Effects of cisapride on anorectal sphincter function. Aliment Pharmacol Ther 1989;3:539–45.

    PubMed  Google Scholar 

  67. Reboa G, Arnulfo G, Frascia M, DiSomma C, Pitto G, Berti-Riboli E. Colon motility and coloanal reflexes in chronic idiopathic constipation: effects of a novel enterokinetic agent cisapride. Eur J Pharmacol 1984;26:745–8.

    Article  Google Scholar 

  68. Sparnon AL, Spitz L. Pharmacological manipulation of postoperative intestinal adhesions. Aust N Z J Surg 1989;59:725–9.

    PubMed  Google Scholar 

  69. Springall RG, Spitz L. The prevention of postoperative adhesions using a gastrointestinal prokinetic agent. J Pediatr Surg 1989;24:530–3.

    PubMed  Google Scholar 

  70. Van Outryve M, Milo R, Toussiant J, Van Eeghem P. Prokinetic treatment of constipation-predominant irritable bowel syndrome: a placebo-controlled study of cisapride. J Clin Gastroenterol 1991;13:49–57.

    PubMed  Google Scholar 

  71. Boghaert A, Haesert G, Mourisse P, Verlinden M. Placebo controlled trial of cisapride in postoperative ileus. Acta Anaesthesiol Belg 1987;38:195–9.

    PubMed  Google Scholar 

  72. Tollesson PO, Cassuto J, Rimback G, Faxen A, Bergman L, Mattson E. Treatment of postoperative ileus with cisapride. Scand J Gastroenterol 1991;26:477–82.

    PubMed  Google Scholar 

  73. Cohen NP, Booth IW, Parashar K, Corkery JJ. Successful management of idiopathic intestinal pseudo-obstruction with cisapride. J Pediatr Surg 1988;23:229–30.

    PubMed  Google Scholar 

  74. Camilleri M, Brown ML, Malagelada JR. Impaired transit of chyme in chronic intestinal pseudo-obstruction: correction by cisapride. Gastroenterology 1986;91:619–26.

    PubMed  Google Scholar 

  75. Hyman PE, McDiarmid SV, Napolitano J, Abrams CE, Tomomasa T. Antroduodenal motility in children with chronic intestinal pseudo-obstruction. J Pediatr 1988;112:899–905.

    PubMed  Google Scholar 

  76. Muller-Lissner SA. Treatment of chronic constipation with cisapride and placebo. Gut 1987;28:1033–8.

    PubMed  Google Scholar 

  77. Hernandez G, Troncoso G, Palencia C, Maldonado S. Double-blind dose response study of cisapride in the treatment of chronic functional constipation. Adv Ther 1988;5:121–7.

    Google Scholar 

  78. Verheyen K, Vervaeke M, Demyttenaere P, Van Mierlo FJ. Double-blind comparison of two cisapride dosage regimens with placebo in the treatment of functional constipation. Curr Ther Res 1987;41:978–85.

    Google Scholar 

  79. Creytens G, Verlinden M, Reyntjens A. Double blind study of cisapride in the treatment of chronic functional, nonspastic constipation. Proceedings of the First International Cisapride Investigators' Meeting, #47.

  80. Hellstrom PM, Aly A, Johansson C. Cisapride stimulates small intestinal motility and relieves constipation in myelopathy due to cervical spinal stenosis: case report. Paraplegia 1990;28:261–4.

    PubMed  Google Scholar 

  81. Staiano A, Cucchiara S, Andreotti MR, Minella R, Manzi G. Effect of cisapride on chronic idiopathic constipation in children. Dig Dis Sci 1991;36:733–6.

    Article  PubMed  Google Scholar 

  82. deGroot GH, dePagter GF. Effects of cisapride on constipation due to a neurological lesion. Paraplegia 1988;26:159–61.

    PubMed  Google Scholar 

  83. Etienne M, Verlinden M, Brassinne A. Treatment with cisapride of the gastrointestinal and urological sequelae of spinal cord transection: case report. Paraplegia 1988;26:162–4.

    PubMed  Google Scholar 

  84. Reyntjens A, Verlinden M, Schrermans V. Safety profile of cisapride. In: Johnson, Lux, eds. Progress in the treatment of gastrointestinal motility disorders: the role of cisapride. Amsterdam: Excerpta Medica, 1988:30–6.

    Google Scholar 

  85. Talley NJ. Review article: 5-hydroxytryptamine agonists and antagonists in the modulation of gastrointestinal motility and sensation: clinical applications. Aliment Pharmacol Ther 1992;6:273–89.

    PubMed  Google Scholar 

  86. Bertaccini G, Coruzzi G. Receptors in the gastrointestinal tract. Pharmacol Res Commun 1987;19:87–118.

    Article  PubMed  Google Scholar 

  87. Willems JL, Bylaert WA, Lefebvre RA, Bogaert MG. Neuronal dopamine receptors on autonomic ganglia and sympathetic nerves and dopamine receptors in the gastrointestinal system. Pharmacol Rev 1985;327:165–216.

    Google Scholar 

  88. Zieba D, Wegrzyn T, Cebrat E, Leroch Z. Effect of dopamine on cecum motility in sheep. Pol Arch Weter 1991;31:109–14.

    PubMed  Google Scholar 

  89. Wiley J, Owyang C. Dopaminergic modulation of rectosigmoid motility: action of domperidone. J Pharmacol Exp Ther 1987;242:548–51.

    PubMed  Google Scholar 

  90. Lanfranchi GA, Marzio L, Cortini C, Osset EM. Motor effect of dopamine on human sigmoid colon: evidence for specific receptors. Dig Dis 1978;23:257–63.

    Article  Google Scholar 

  91. Laduron PM, Leysen JE. Domperidone, a specific in vitro dopamine antagonist, devoid of in vivo central dopaminergic activity. Biochem Pharmacol 1979;28:2161–5.

    Article  PubMed  Google Scholar 

  92. Brogden RN, Carmine AA, Heel RC,et al. Domperidone: a review of its pharmacological activity, pharmacokinetics and therapeutic efficacy in the symptomatic treatment of chronic dyspepsia and as an antiemetic. Drugs 1982;24:360–400.

    PubMed  Google Scholar 

  93. Jay GT, Feldman TA. Focus on domperidone: a selective dopamine antagonist for diabetic gastroparesis and idiopathic gastric stasis. Hosp Formul 1991;26:171–83.

    Google Scholar 

  94. Bron B, Massih L. Domperidone: a drug with powerful action on the lower esophageal sphincter pressure. Digestion 1980;20:375–8.

    PubMed  Google Scholar 

  95. Schulze-Delrieu K, Summers RW, Fink D. Domperidone in reflux esophagitis and gastric stasis. Lancet 1981;1:159.

    Article  Google Scholar 

  96. Platteborse R, Hermans C, Loots W,et al. The effect of domperidone on pyloric activity in dog and in man. Postgrad Med J 1979;55(Suppl 1):15–8.

    Google Scholar 

  97. Schuurkes JA, Van Nueten JM, Van Daele PG,et al. Domperidone improves myogenically transmitted antroduodenal coordination by blocking dopaminergic receptor sites. Scand J Gastroenterol 1984; (Suppl 96):101–10.

    Google Scholar 

  98. Albibi R, DuBovic S, Lange RC,et al. A dose response study of the effects of domperidone on gastric retention states in man. Am J Gastroenterol 1983;78:679.

    Google Scholar 

  99. Baeyens R, Van DeVelde E, DeSchepper A,et al. Effects of intravenous and oral domperidone on the motor function of the stomach and small intestine. Postgrad Med J 1979;55(Suppl 1):19–23.

    Google Scholar 

  100. Horowitz M, Harding PE, Chatterton BE,et al. Acute and chronic effects of domperidone on gastric emptying in diabetes and autonomic neuropathy. Dig Dis Sci 1985;30:1–9.

    Article  PubMed  Google Scholar 

  101. McCallum RW, Ricci D, DuBovic S,et al. Effect of domperidone on gastric emptying and symptoms in patients with idiopathic gastric stasis (abstr). Gastroenterology 1984;5.

  102. Lanfranchi GA, Bazzocchi G, Fois F, Brignola C, Campieri M, Menni B. Effect of domperidone on colonie motor activity in patients with the irritable bowel syndrome. Eur J Clin Pharmacol 1985;29:307–10.

    Article  PubMed  Google Scholar 

  103. Cann PA, Read NW, Holdsworth CD. Oral domperidone: double blind comparison with placebo in irritable bowel syndrome. Gut 1983;12:1135–40.

    Google Scholar 

  104. Sowers JR, Sharp B, McCallum RW. Effect of domperidone, an extracerebral inhibitor of dopamine receptors, on thyrotropin, prolactin, renin, aldosterone and 18-hydroxycortisone secretion in man. J Clin Endocrinol Metab 1982;54:869–71.

    PubMed  Google Scholar 

  105. Brown JC, Cook MA, Dryburgh JR. Motilin, a gastric motor activity-stimulating polypeptide: the complete amino acid sequence. Can J Biochem 1972;51:533–7.

    Google Scholar 

  106. Polak JM, Pearse AG, Heath CM. Complete identification of endocrine cells in the gastrointestinal tract using semithin sections to identify motilin cells in human and animal intestine. Gut 1975;16:225.

    PubMed  Google Scholar 

  107. Mitzness P, Bloom SR, Domschke W, Domschke S, Wunsch E, Demling L. Release of motilin after duodenal acidification. Lancet 1976;1:888–9.

    Article  PubMed  Google Scholar 

  108. Itoh Z, Aizawa I, Talceuchi S, Couch EF. Hunger contractions and motilin. In: Van Trappen G, ed. Proceedings of the 5th International Symposium on Gastrointestinal Motility. Heventals, Belgium: Typoff-Press, 1976:48–55.

    Google Scholar 

  109. Itoh Z, Takahashi I, Nakaya M. Interdigestive contractions in the gallbladder controlled by motilin. Regul Pept 1980;(Suppl 1):555.

    Google Scholar 

  110. Zara GP, Thompson HH, Pilot MA, Ritchie HD. Effects of erythromycin on gastrointestinal tract motility. J Antimicrob Chem 1985;16(Suppl A):175–9.

    PubMed  Google Scholar 

  111. Pilot MA, Ritchie HD, Thompson H, Zara GP. Alterations in gastrointestinal motility associated with erythromycin (abstr). Br J Pharmacol 1984;81:168P.

    Google Scholar 

  112. Itoh Z, Nakaya M, Suzuki T, Arai H, Wakabayashi K. Erythromycin mimics exogenous motilin in gastrointestinal contractile activity in the dog. Am J Physiol 1984;247(Gastrointest Liver Physiol 10):G688–94.

    PubMed  Google Scholar 

  113. Kondo KT, Torii S, Omura S, Itoh Z. Erythromycin and its derivatives with motilin-like biological activities inhibit the specific binding of125I-motilin to duodenal muscle. Biochem Biophys Res Commun 1988;150:877–82.

    Article  PubMed  Google Scholar 

  114. Peeters T, Matthijis G, Depoortere I, Cachet T, Hoogmartens J, Van Trappen G. Erythromycin is a motilin receptor agonist. Am J Physiol 1989;257(Gastrointest Liver Physiol 20):G470–4.

    PubMed  Google Scholar 

  115. Depoortere I, Peeters TL, Matthijs G, Van Trappen G. Macrolide antibiotics are motilin receptor agonists. Hepatogastroenterology 1988;35:198.

    Google Scholar 

  116. Minocha A, Galligan JJ. Erythromycin inhibits contractions of nerve muscle preparations of guinea pig small intestine. J Pharmacol Exp Ther 1991;257:1248–52.

    PubMed  Google Scholar 

  117. Armstrong DN, Ballantyne GH, Modlin IM. Erythromycin stimulates ileal motility by activation of dihydropyridine-sensitive calcium channels. J Surg Res 1992;52:140–6.

    Article  PubMed  Google Scholar 

  118. Inatomi N, Satoh H, Maki Y, Hashimoto N, Itoh Z, Omura S. An erythromycin derivative, EM-523, induces motilin like gastrointestinal motility in dogs. J Pharmacol Exp Ther 1989;251:707–12.

    PubMed  Google Scholar 

  119. Hasler WL, Heldsinger A, Owyang C. Erythromycin contracts rabbit colon myocytes via occupation of motilin receptors. Am J Physiol 1992;262(Gastrointest Liver Physiol 25):G50–5.

    PubMed  Google Scholar 

  120. Hasler W, Heldsinger A, Soudah H, Onyang C. Erythromycin promotes colonic transit in humans: mediation via motilin receptors. Gastroenterology 1990;98:A358.

    Google Scholar 

  121. Tomomasa T, Kuroume T, Arai H, Wakabayashi K, Itoh Z. Erythromycin induces migrating motor complex in human gastrointestinal tract. Dig Dis Sci 1986;31:157–61.

    Article  PubMed  Google Scholar 

  122. Janssens J, Peeters TL, Van Trappen G,et al. Improvement of gastric emptying in diabetic gastroparesis by erythromycin: preliminary studies. N Engl J Med 1990;322:1028–31.

    PubMed  Google Scholar 

  123. Armstrong DN, Ballantyne GH, Modlin IM. Erythromycin for reflex ileus in Ogilvie's syndrome. Lancet 1991;337:1991.

    Article  Google Scholar 

  124. Miller SM, O'Dorsio TM, Thomas FB, Mekhjian HS. Erythromycin exerts a prokinetic effect in patients with chronic idiopathic intestinal pseudo-obstruction. Gastroenterology 1990;98:A375.

    Google Scholar 

  125. Sjolund K, Ekman R, Akre F, Linder P. Motilin in chronic idiopathic constipation. Scand J Gastroenterol 1986;21:914–8.

    PubMed  Google Scholar 

  126. Jaffe JH, Martin WR. Opioid analgesics and antagonists. In: Gilman AG, Goodman LS, Rall TW, Murad F, eds. The pharmacological basis of therapeutics. New York: MacMillan, 1985:491–531.

    Google Scholar 

  127. Kreuger H. The action of morphine on the digestive tract. Physiol Rev 1937;17:619–45.

    Google Scholar 

  128. Konturek SJ. Opiates and the gastrointestinal tract. Am J Gastroenterol 1980;74:285–91.

    PubMed  Google Scholar 

  129. Kaufman PN, Krevsky B, Malmud LS,et al. Role of opiate receptors in the regulation of colonic transit. Gastroenterology 1988;94:1351–6.

    PubMed  Google Scholar 

  130. Ruoff HJ, Fladung B, Demol P, Weihrauch TR. Gastrointestinal receptors and drugs in motility disorders. Digestion 1991;48:1–17.

    PubMed  Google Scholar 

  131. Burks TF. Actions of drugs on gastrointestinal motility. In: Johnson LR, ed. Physiology of the gastrointestinal tract. Vol. 1. New York: Raven Press, 1987:723–43.

    Google Scholar 

  132. Schang JC, Devroede G, Perrault R. Naloxone therapy in small intestinal pseudo-obstruction: preliminary results about two cases. Am J Gastroenterol 1984;79:828.

    Google Scholar 

  133. Kling N. Naloxone in opiate-induced colonic pseudo-obstruction. S Afr Med J 1991;79:53.

    Google Scholar 

  134. Kreek MJ, Schaefer RA, Hahn EF, Fishman J. Naloxone, a specific opioid antagonist, reverses chronic idiopathic constipation. Lancet 1983;1:261–2.

    Article  PubMed  Google Scholar 

  135. Kreek MJ, Paris P, Bartol MA, Mueller D. Effects of short term administration of the specific opioid antagonist naloxone on fecal evacuation in geriatric patients. Gastroenterology 1984;86:1144A.

    Google Scholar 

  136. Fotherby KJ, Hunter JO. Idiopathic slow-transit constipation: whole gut transit times, measured by a new simplified method, are not shortened by opioid antagonists. Aliment Pharmacol Ther 1987;1:331–8.

    PubMed  Google Scholar 

  137. Kreek MJ, Marsh F, Kutscher J, Schmugier J, Connor B, Schaefer RA. Effects of short term administration of naloxone on fecal evacuation in patients with idiopathic chronic constipation and irritable bowel syndrome. Gastroenterology 1985;88:1457A.

    Google Scholar 

  138. Katz MD, Erstad BL. Octreotide, a new somatostatin analogue. Clin Pharm 1989;8:255–73.

    PubMed  Google Scholar 

  139. Lux G, Femppel J, Lederer P, Rosch W, Domschke W. Somatostatin induces interdigestive intestinal motor and secretory complex-like activity in man. Gastroenterology 1980;78:A1212.

    Google Scholar 

  140. Peeters TL, Janssens J, Van Trappen FT. Somatostatin and the interdigestive migrating motor complex in man. Regul Pept 1983;5:209–17.

    Article  PubMed  Google Scholar 

  141. Hartsock M, Little AG. Somatostatin stimulation of the normal esophagus. Am J Surg 1992;163:159–62.

    Google Scholar 

  142. Richards WO, Geer R, O'Dorisio TM,et al. Octreotide acetate induces fasting small bowel motility in patients with dumping syndrome. J Surg Res 1990;49:483–7.

    Article  PubMed  Google Scholar 

  143. Soudah HC, Hasler WL, Owyang C. Effect of octreotide on intestinal motility and bacterial overgrowth in scleroderma. N Engl J Med 1991;325:1508–9.

    PubMed  Google Scholar 

  144. Cullen JJ, Eagon JC, Dozois EJ, Kelly KA. Treatment of acute postoperative ileus with octreotide. Am J Surg 1993;165:113–9.

    PubMed  Google Scholar 

  145. Soudah HC, Hasler WL, Owyang C. Somatostatin analog stimulates rectosigmoid motility and promotes colonic transit in humans via a cholinergic pathway. Gastroenterology 1991;180:A497.

    Google Scholar 

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  1. Department of Surgery, Section of Colon and Rectal Surgery, St. Louis University School of Medicine, St. Louis, Missouri

    Walter E. Longo M.D. & Anthony M. Vernava III M.D.

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  1. Walter E. Longo M.D.
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  2. Anthony M. Vernava III M.D.
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Longo, W.E., Vernava, A.M. Prokinetic agents for lower gastrointestinal motility disorders. Dis Colon Rectum 36, 696–708 (1993). https://doi.org/10.1007/BF02238599

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