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

Abstract

ton, and Alan R. Zinsmeister. Effects of a -opioid agonist, asimadoline, on satiation and GI motor and sensory functions in humans. Am J Physiol Gastrointest Liver Physiol 284: G558-G566, 2003; 10.1152 10. /ajpgi.00360.2002pare the effects of the -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 ϭ 0.03). Asimadoline decreased colonic tone during fasting (P ϭ 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 ϭ 0.04) but not at higher levels of distension. Asimadoline at 1.5 mg increased gas scores at 16 mmHg of distension (P ϭ 0.03) and pain scores at distensions of 8 and 16 mmHg (P ϭ 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 VISCERAL PAIN AND DISCOMFORT are relevant clinical features of many medical processes, including functional gastrointestinal (GI) disorders (57). These are frequent and chronic-relapsing conditions with a great impact on quality of life (23), yet no satisfactory treatment is available for treatment of pain in these highly prevalent conditions.The three major opioid receptors, , ␦, and , are distributed in the peripheral and central nervous systems (45, 53) and are known to modulate visceral nociception (16,22,29).

Prospective Study of Motor, Sensory, Psychologic, and Autonomic Functions in Patients With Irritable Bowel Syndrome

“…In our study, the threshold for pain was defined as the first pressure that was associated with experience of pain, and all studies were performed over a 3-year period by one technologist (IB). The term "threshold" is defined as "the point at which a physiological or psychological effect begins to be produced" (Webster's New Collegiate Dictionary), and we have applied this definition in several studies in the literature (35,36). In contrast, other papers in the literature defined "threshold" as grade 3/5 on the pain scale (37,38) or 3/10 on the discomfort scale (8) for the individual patient.…”

Satiety testing: Ready for the clinic?

“…A similar study also found no effect on maximal ingested volume or symptoms in healthy subjects treated with either citalopram, desipramine or placebo for 11 d [18] . In contrast, in healthy subjects, the kappa-opioid agonist asimadoline has been shown to increase maximal tolerated volumes without altering gastric emptying [19] . A small trial randomized patients with functional dyspepsia to biofeedback (breathing exercises using software for vagal biofeedback) or an educational control group [20] .…”

Novel Orally Available Salvinorin A Analog PR-38 Inhibits Gastrointestinal Motility and Reduces Abdominal Pain in Mouse Models Mimicking Irritable Bowel Syndrome

“…Recently, broader attention has been given to KORs and their ligands, which may become a target in the treatment of GI disorders, such as postoperative ileus, irritable bowel syndrome (IBS), and intestinal inflammation (Fichna et al, 2009a). Clinical trials with a peripherally acting KOR agonist, asimadoline, are particularly encouraging in patients with IBS (Delgado-Aros et al, 2003;Camilleri, 2008), as they proved that asimadoline decreases pain and improves abnormal bowel function.…”