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. 1994 Apr;35(4):496–500. doi: 10.1136/gut.35.4.496

5-Hydroxytryptamine and human small intestinal motility: effect of inhibiting 5-hydroxytryptamine reuptake.

D A Gorard 1, G W Libby 1, M J Farthing 1
PMCID: PMC1374798  PMID: 8174987

Abstract

Parenteral 5-hydroxytryptamine stimulates small intestinal motility, but the effect of continuous stimulation with 5-hydroxytryptamine on the human migrating motor complex is unknown. Using a selective 5-hydroxytryptamine reuptake inhibitor, paroxetine, this study investigated the effect of indirect 5-hydroxytryptamine agonism on fasting small intestinal motility and transit. Eight healthy subjects were studied while receiving paroxetine 30 mg daily for five days and while receiving no treatment, in random order. Ambulant small intestinal motility was recorded from five sensors positioned from the duodenojejunal flexure to the ileum for 16-18 hours. Paroxetine reduced the migrating motor complex periodicity mean (SEM) from 81 (6) min to 67 (4) min (p < 0.05), and increased the propagation velocity of phase III from 3.1 to 4.7 cm/min in the proximal jejunum (p < 0.01), and from 1.6 to 3.4 cm/min distally (p < 0.001). Orocaecal transit time measured by lactulose hydrogen breath test was reduced by paroxetine from 70 (9) min to 48 (7) min (p < 0.05). These data suggest that 5-hydroxytryptamine participates in the control of migrating motor complexes in humans, and that selective 5-hydroxytryptamine reuptake inhibitors have a prokinetic action in the human small intestine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Akkermans L. M., Vos A., Hoekstra A., Roelofs J. M., Horowitz M. Effect of ICS 205-930 (a specific 5-HT3 receptor antagonist) on gastric emptying of a solid meal in normal subjects. Gut. 1988 Sep;29(9):1249–1252. doi: 10.1136/gut.29.9.1249. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Borody T. J., Quigley E. M., Phillips S. F., Wienbeck M., Tucker R. L., Haddad A., Zinsmeister A. R. Effects of morphine and atropine on motility and transit in the human ileum. Gastroenterology. 1985 Sep;89(3):562–570. doi: 10.1016/0016-5085(85)90452-4. [DOI] [PubMed] [Google Scholar]
  3. Coelho J. C., Gouma D. J., Moody F. G., Li Y. F., Weisbrodt N. W. Serotonin increases the velocity of propagation and frequency of the migrating myoelectric complexes. Eur J Clin Invest. 1986 Jun;16(3):252–256. doi: 10.1111/j.1365-2362.1986.tb01338.x. [DOI] [PubMed] [Google Scholar]
  4. Costall B., Naylor R. J. 5-Hydroxytryptamine: new receptors and novel drugs for gastrointestinal motor disorders. Scand J Gastroenterol. 1990 Aug;25(8):769–787. doi: 10.3109/00365529008999215. [DOI] [PubMed] [Google Scholar]
  5. Dechant K. L., Clissold S. P. Paroxetine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness. Drugs. 1991 Feb;41(2):225–253. doi: 10.2165/00003495-199141020-00007. [DOI] [PubMed] [Google Scholar]
  6. Di Lorenzo C., Dooley C. P., Valenzuela J. E. Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test. Gut. 1991 Oct;32(10):1127–1130. doi: 10.1136/gut.32.10.1127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gershon M. D., Jonakait G. M. Uptake and release of 5-hydroxytryptamine by enteric 5-hydroxytryptaminergic neurones: effects of fluoxetine (Lilly 110140) and chlorimipramine. Br J Pharmacol. 1979 May;66(1):7–9. doi: 10.1111/j.1476-5381.1979.tb16089.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gershon M. D., Sherman D. L. Noradrenergic innervation of serotoninergic neurons in the myenteric plexus. J Comp Neurol. 1987 May 8;259(2):193–210. doi: 10.1002/cne.902590203. [DOI] [PubMed] [Google Scholar]
  9. Gershon M. D., Wade P. R., Kirchgessner A. L., Tamir H. 5-HT receptor subtypes outside the central nervous system. Roles in the physiology of the gut. Neuropsychopharmacology. 1990 Oct-Dec;3(5-6):385–395. [PubMed] [Google Scholar]
  10. Gore S., Gilmore I. T., Haigh C. G., Brownless S. M., Stockdale H., Morris A. I. Colonic transit in man is slowed by ondansetron (GR38032F), a selective 5-hydroxytryptamine receptor (type 3) antagonist. Aliment Pharmacol Ther. 1990 Apr;4(2):139–144. doi: 10.1111/j.1365-2036.1990.tb00458.x. [DOI] [PubMed] [Google Scholar]
  11. HAVERBACK B. J., DAVIDSON J. D. Serotonin and the gastrointestinal tract. Gastroenterology. 1958 Dec;35(6):570–578. [PubMed] [Google Scholar]
  12. HENDRIX T. R., ATKINSON M., CLIFTON J. A., INGELFINGER F. J. The effect of 5-hydroxytryptamine on intestinal motor function in man. Am J Med. 1957 Dec;23(6):886–893. doi: 10.1016/0002-9343(57)90298-x. [DOI] [PubMed] [Google Scholar]
  13. Hopkinson G. B., Hinsdale J., Jaffe B. M. Contraction of canine stomach and small bowel by intravenous administration of serotonin. A physiologic response? Scand J Gastroenterol. 1989 Oct;24(8):923–932. doi: 10.3109/00365528909089236. [DOI] [PubMed] [Google Scholar]
  14. Kellow J. E., Borody T. J., Phillips S. F., Tucker R. L., Haddad A. C. Human interdigestive motility: variations in patterns from esophagus to colon. Gastroenterology. 1986 Aug;91(2):386–395. doi: 10.1016/0016-5085(86)90573-1. [DOI] [PubMed] [Google Scholar]
  15. Kellow J. E., Gill R. C., Wingate D. L. Prolonged ambulant recordings of small bowel motility demonstrate abnormalities in the irritable bowel syndrome. Gastroenterology. 1990 May;98(5 Pt 1):1208–1218. doi: 10.1016/0016-5085(90)90335-x. [DOI] [PubMed] [Google Scholar]
  16. Kerlin P., Phillips S. Variability of motility of the ileum and jejunum in healthy humans. Gastroenterology. 1982 Apr;82(4):694–700. [PubMed] [Google Scholar]
  17. Labo G., Barbara L., Lanfranchi G. A., Bortolotti M., Miglioli M. MOdification of the electrical activity of the human intestine after serotonin and caerulein. Am J Dig Dis. 1972 Apr;17(4):363–372. doi: 10.1007/BF02231739. [DOI] [PubMed] [Google Scholar]
  18. Lederer P. C., Thiemann R., Femppel J., Domschke W., Lux G. Influence of atropine, pirenzepine and cimetidine on nocturnal gastro-intestinal motility and gastric acid secretion. Scand J Gastroenterol Suppl. 1982;72:131–137. [PubMed] [Google Scholar]
  19. McIntyre A. S., Thompson D. G., Burnham W. R., Walker E. The effect of alpha-1-adrenoreceptor agonist and antagonist administration on human upper gastrointestinal transit and motility. Aliment Pharmacol Ther. 1992 Aug;6(4):415–426. doi: 10.1111/j.1365-2036.1992.tb00555.x. [DOI] [PubMed] [Google Scholar]
  20. McIntyre A. S., Thompson D. G., Day S., Burnham W. R., Walker E. R. Modulation of human upper intestinal nutrient transit by a beta adrenoreceptor mediated pathway. Gut. 1992 Aug;33(8):1062–1070. doi: 10.1136/gut.33.8.1062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Misiewicz J. J., Waller S. L., Eisner M. Motor responses of human gastrointestinal tract to 5-hydroxytryptamine in vivo and in vitro. Gut. 1966 Jun;7(3):208–216. doi: 10.1136/gut.7.3.208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ormsbee H. S., 3rd, Silber D. A., Hardy F. E., Jr Serotonin regulation of the canine migrating motor complex. J Pharmacol Exp Ther. 1984 Nov;231(2):436–440. [PubMed] [Google Scholar]
  23. Piñeiro-Carrero V. M., Clench M. H., Davis R. H., Andres J. M., Franzini D. A., Mathias J. R. Intestinal motility changes in rats after enteric serotonergic neuron destruction. Am J Physiol. 1991 Feb;260(2 Pt 1):G232–G239. doi: 10.1152/ajpgi.1991.260.2.G232. [DOI] [PubMed] [Google Scholar]
  24. Ruckebusch Y., Bardon T. Involvement of serotonergic mechanisms in initiation of small intestine cyclic motor events. Dig Dis Sci. 1984 Jun;29(6):520–527. doi: 10.1007/BF01296272. [DOI] [PubMed] [Google Scholar]
  25. Sagrada A., Brancaccio N., Schiavone A. 5-Hydroxytryptamine affects rat migrating myoelectric complexes through different receptor subtypes: evidence from 5-hydroxytryptophan administration. Life Sci. 1990;46(17):1207–1216. doi: 10.1016/0024-3205(90)90495-d. [DOI] [PubMed] [Google Scholar]
  26. Sarna S. K. Cyclic motor activity; migrating motor complex: 1985. Gastroenterology. 1985 Oct;89(4):894–913. doi: 10.1016/0016-5085(85)90589-x. [DOI] [PubMed] [Google Scholar]
  27. Sninsky C. A., Davis R. H., Clench M. H., Thomas K. D., Mathias J. R. Effect of lidamidine hydrochloride and loperamide on gastric emptying and transit of the small intestine. A double-blind study. Gastroenterology. 1986 Jan;90(1):68–73. doi: 10.1016/0016-5085(86)90076-4. [DOI] [PubMed] [Google Scholar]
  28. Szurszewski J. H. A migrating electric complex of canine small intestine. Am J Physiol. 1969 Dec;217(6):1757–1763. doi: 10.1152/ajplegacy.1969.217.6.1757. [DOI] [PubMed] [Google Scholar]
  29. Talley N. J., Phillips S. F., Haddad A., Miller L. J., Twomey C., Zinsmeister A. R., Ciociola A. Effect of selective 5HT3 antagonist (GR 38032F) on small intestinal transit and release of gastrointestinal peptides. Dig Dis Sci. 1989 Oct;34(10):1511–1515. doi: 10.1007/BF01537102. [DOI] [PubMed] [Google Scholar]
  30. Thomas D. R., Nelson D. R., Johnson A. M. Biochemical effects of the antidepressant paroxetine, a specific 5-hydroxytryptamine uptake inhibitor. Psychopharmacology (Berl) 1987;93(2):193–200. doi: 10.1007/BF00179933. [DOI] [PubMed] [Google Scholar]
  31. Vantrappen G., Janssens J., Hellemans J., Ghoos Y. The interdigestive motor complex of normal subjects and patients with bacterial overgrowth of the small intestine. J Clin Invest. 1977 Jun;59(6):1158–1166. doi: 10.1172/JCI108740. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yoshida N., Mizumoto A., Iwanaga Y., Itoh Z. Effects of 5-hydroxytryptamine 3 receptor antagonists on gastrointestinal motor activity in conscious dogs. J Pharmacol Exp Ther. 1991 Jan;256(1):272–278. [PubMed] [Google Scholar]

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