Effects of asimadoline, a kappa-opioid agonist, on satiation and postprandial symptoms in health.
OBJECTIVE
To evaluate the effect of single administrations of asimadoline, a kappa-opioid agonist, on satiation volume, postprandial symptoms and gastric volumes.


METHODS
Healthy subjects received oral placebo, or 0.5 or 1.5 mg asimadoline in a randomized, double-blind fashion 1 h prior to testing. We assessed effects on the volume of Ensure to achieve full satiation and postprandial symptoms 30 min after meal, and on gastric volume (fasting and postprandial) measured by 99mTc-single photon emission tomography (SPECT) imaging.


RESULTS
Thirteen healthy subjects were studied in each treatment arm. Compared to placebo, asimadoline 0.5 mg decreased postprandial fullness (P = 0.027) without affecting the volume ingested at full satiation (P = 0.6). Asimadoline 1.5 mg decreased satiation during meal, allowing increased satiation volumes (P = 0.008) and tended to decrease postprandial fullness (P = 0.067), despite higher volumes ingested. There was a significant treatment-gender interaction in the effect of asimadoline on gastric volumes (P < 0.05). Asimadoline 0.5 mg (not 1.5 mg) increased fasting (P = 0.047) and postprandial (P = 0.009) gastric volumes in females but decreased fasting volumes in males (P = 0.008). The effect of asimadoline on gastric volume did not explain the effect observed on satiation volume (P = 0.371) or postprandial fullness (P = 0.399).


CONCLUSIONS
A single oral administration of asimadoline decreases satiation and postprandial fullness in humans independently of its effects on gastric volume.
Delgado-Aros
S
S
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, Mayo Clinic, Rochester, MN 55905, USA.
Chial
H J
HJ
Cremonini
F
F
Ferber
I
I
McKinzie
S
S
Burton
D D
DD
Camilleri
M
M
D000081:Acetamides / Q000008:administration & dosage / Q000494:pharmacology*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011759:Pyrrolidines / Q000008:administration & dosage / Q000494:pharmacology*; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*; D012527:Satiation / Q000187:drug effects*; D013670:Sodium Pertechnetate Tc 99m; D013270:Stomach / Q000000981:diagnostic imaging; D015899:Tomography, Emission-Computed, Single-Photon
D000081:Acetamides; D011759:Pyrrolidines; D019275:Radiopharmaceuticals; D017473:Receptors, Opioid, kappa; D013670:Sodium Pertechnetate Tc 99m; C092095:asimadoline