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Effects of a kappa-opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans.

Abstract
To compare the effects of the kappa-opioid agonist asimadoline and placebo on visceral sensation and gastrointestinal (GI) motor functions in humans, 91 healthy participants were randomized in a double-blind fashion to 0.15, 0.5, or 1.5 mg of asimadoline or placebo orally twice a day for 9 days. We assessed satiation (nutrient drink test), colonic compliance, tone, perception of colonic distension (barostat), and whole gut transit (scintigraphy). Treatment effect was assessed by analysis of covariance. Asimadoline increased nutrient drink intake (P = 0.03). Asimadoline decreased colonic tone during fasting (P = 0.03) without affecting postprandial colonic contraction, compliance, or transit. Gas scores in response to colonic distension were decreased with 0.5 mg of asimadoline at low levels (8 mmHg above operating pressure) of distension (P = 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension (P = 0.03) and pain scores at distensions of 8 and 16 mmHg (P = 0.003 and 0.03, respectively) but not at higher levels of distension. Further studies of this compound in diseases with altered satiation or visceral sensation are warranted.
AuthorsSilvia Delgado-Aros, Heather J Chial, Michael Camilleri, Lawrence A Szarka, Frank T Weber, Jutta Jacob, Irene Ferber, Sanna McKinzie, Duane D Burton, Alan R Zinsmeister
JournalAmerican journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 284 Issue 4 Pg. G558-66 (Apr 2003) ISSN: 0193-1857 [Print] United States
PMID12631557 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Acetamides
  • Pyrrolidines
  • Receptors, Opioid, kappa
  • asimadoline
Topics
  • Acetamides (administration & dosage, adverse effects)
  • Adolescent
  • Adult
  • Colon (drug effects, innervation, physiology)
  • Compliance (drug effects)
  • Double-Blind Method
  • Female
  • Flatulence (drug therapy)
  • Gastrointestinal Motility (drug effects)
  • Humans
  • Male
  • Middle Aged
  • Pain (drug therapy)
  • Postprandial Period (drug effects)
  • Pyrrolidines (administration & dosage, adverse effects)
  • Receptors, Opioid, kappa (agonists)
  • Satiation (drug effects)
  • Sensation (drug effects)
  • Stomach (drug effects, innervation, physiology)
  • Visceral Afferents (drug effects, physiology)

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