Effect of the NK3 receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans

L. A. Houghton, F. Cremonini, Michael Camilleri, I. Busciglio, C. Fell, V. Cox, D. H. Alpers, O. E. Dewit, G. E. Dukes, E. Gray, R. Lea, A. R. Zinsmeister, P. J. Whorwell

Research output: Contribution to journalArticle

41 Scopus citations

Abstract

Visceral hypersensitivity is important in the pathophysiology of irritable bowel syndrome and thus a target for modulation in drug development. Neurokinin (NK) receptors, including NK3 receptors, are expressed in the motor and sensory systems of the digestive tract. The aim of this study was to compare the effects of two different doses (25 and 100 mg) of the NK3 receptor antagonist, talnetant (SB223412) with placebo on rectal sensory function and compliance in healthy volunteers studied at two centres. Rectal barostat tests were performed on 102 healthy volunteers, randomized to receive either oral talnetant 25 or 100 mg or placebo over 14-17 days. Studies were performed on three occasions: day 1 immediately prior to 1st dose, day 1 4 h postdose, and after 14- to17-day therapy. Compliance, and pressure thresholds for first sensation, urgency, discomfort and pain were measured using ascending method of limits, and sensory intensity ratings for gas, urgency, discomfort and pain determined during four random phasic distensions (12, 24, 36 and 48 mmHg). Talnetant had no effect on rectal compliance, sensory thresholds or intensity ratings compared with placebo. In general, the results obtained at the two centres differed minimally, with intensity scores at one centre consistently somewhat lower. At the doses tested, talnetant has no effect on rectal compliance or distension-induced rectal sensation in healthy participants.

Original languageEnglish (US)
Pages (from-to)732-743
Number of pages12
JournalNeurogastroenterology and Motility
Volume19
Issue number9
DOIs
StatePublished - Sep 2007

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Keywords

  • Antagonist
  • Ascending method of limits
  • Neurokinin
  • Perception
  • Sensory intensity ratings
  • Visceral

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology
  • Neuroscience(all)

Cite this

Houghton, L. A., Cremonini, F., Camilleri, M., Busciglio, I., Fell, C., Cox, V., Alpers, D. H., Dewit, O. E., Dukes, G. E., Gray, E., Lea, R., Zinsmeister, A. R., & Whorwell, P. J. (2007). Effect of the NK3 receptor antagonist, talnetant, on rectal sensory function and compliance in healthy humans. Neurogastroenterology and Motility, 19(9), 732-743. https://doi.org/10.1111/j.1365-2982.2007.00934.x