Efficacy of on-demand asimadoline, a peripheral kappa-opioid agonist, in females with irritable bowel syndrome.
OBJECTIVE
In experimental animal models of irritable bowel syndrome (IBS) and human studies, peripheral kappa opioid agonists have been shown to decrease sensation to colonic distention. The aim of this study was to compare the effects of the kappa opioid agonist, asimadoline, and placebo on episodes of abdominal pain in patients with IBS.


METHODS
After a 2-week run-in period, 100 patients with IBS were randomized (3:2 ratio) to receive asimadoline, up to 1 mg 4 times daily, or placebo for 4 weeks in a double-blind study. Pain was scored by daily diary using a 100-mm visual analogue scale. During pain episodes, patients recorded the pain severity, took study medication, and recorded their pain score 2 hours later. The primary end point was the average reduction in pain severity 2 hours after treatment.


RESULTS
The average pain reduction 2 hours posttreatment was not significantly different between the groups. Post hoc analyses suggest asimadoline was effective in mixed IBS (P = .003, unadjusted), but may be worse in diarrhea-predominant IBS (P = .065 unadjusted). The anxiety score was reduced modestly by asimadoline (P = .053). No significant adverse effects were noted.


CONCLUSIONS
An on-demand dosing schedule of asimadoline was not effective in reducing severity of abdominal pain in IBS. Further studies in visceral pain and IBS appear warranted.
Szarka
Lawrence A
LA
Clinical Enteric Neuroscience Translational and Epidemiological Research (CENTER) Program, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Camilleri
Michael
M
Burton
Duane
D
Fox
Jean C
JC
McKinzie
Sanna
S
Stanislav
Timothy
T
Simonson
Julie
J
Sullivan
Nancy
N
Zinsmeister
Alan R
AR
D000081:Acetamides / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001007:Anxiety / Q000188:drug therapy; D003863:Depression / Q000188:drug therapy; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy* / Q000523:psychology; D008875:Middle Aged; D010147:Pain Measurement; D011759:Pyrrolidines / Q000627:therapeutic use*; D011788:Quality of Life; D017473:Receptors, Opioid, kappa / Q000819:agonists*
D000081:Acetamides; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; C092095:asimadoline