Asimadoline is a potent
kappa-opioid receptor agonist with a diaryl
acetamide structure. It has high affinity for the
kappa receptor, with IC(50) of 5.6 nmol L(-1) (guinea pig) and 1.2 nmol L(-1) (human recombinant), and high selectively with kappa : micro : delta binding ratios of 1 : 501 : 498 in human recombinant receptors. It acts as a complete agonist in in vitro assay.
Asimadoline reduced sensation in response to colonic distension at subnoxious pressures in healthy volunteers and in
irritable bowel syndrome (IBS) patients without alteration of colonic compliance.
Asimadoline reduced satiation and enhanced the postprandial gastric volume (in female volunteers). However, there were no significant effects on gastrointestinal transit, colonic compliance, fasting or postprandial colonic tone. In a clinical trial in 40 patients with functional
dyspepsia (Rome II),
asimadoline did not significantly alter satiation or symptoms over 8 weeks. However,
asimadoline, 0.5 mg, significantly decreased satiation in patients with higher postprandial fullness scores, and daily postprandial fullness severity (over 8 weeks); the
asimadoline 1.0 mg group was borderline significant. In a clinical trial in patients with IBS, average
pain 2 h post-on-demand treatment with
asimadoline was not significantly reduced. Post hoc analyses suggest that
asimadoline was effective in mixed IBS. In a 12-week study in 596 patients, chronic treatment with 0.5 mg and 1.0 mg
asimadoline was associated with adequate relief of
pain and discomfort, improvement in
pain score and number of
pain-free days in patients with IBS-D. The 1.0 mg dose was also efficacious in IBS-alternating. There were also weeks with significant reduction in bowel frequency and urgency.
Asimadoline has been well tolerated in human trials to date.