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Am J Physiol Gastrointest Liver Physiol 284: G558-G566, 2003; doi:10.1152/ajpgi.00360.2002
0193-1857/03 $5.00
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Vol. 284, Issue 4, G558-G566, April 2003

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

Silvia Delgado-Aros1, Heather J. Chial1, Michael Camilleri1, Lawrence A. Szarka1, Frank T. Weber3, Jutta Jacob3, Irene Ferber1, Sanna McKinzie1, Duane D. Burton1, and Alan R. Zinsmeister2

1 Clinical Enteric Neuroscience Translational and Epidemiological Research Program and 2 Division of Biostatistics, Mayo Clinic, Rochester, Minnesota 55905; and 3 Merck KGaA, Darmstadt, Germany

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.

sensation; visceral; stomach; colon; barostat


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