Abstract
Background: β3-adrenoceptors (β3-AR) are expressed in adipocytes, heart, skeletal muscle, and smooth muscle. Agonists of β3-AR reduce the elevated tone and inhibit spontaneous contractions in the human isolated colon, but the exact site of action is not clear. β3-AR expression is co-localized with choline acetyl transferase (ChAT) in a majority of the neurons in human colonicmyenteric and submucosal plexus. Human selective β3-AR agonist, solabegron, inhibits cholinergic contractions and enhances release of somatostatin with no effect on carbachol-induced contractions in human isolated colon. A rodent selective β3-AR agonist inhibits castor oil-induced diarrhea in rats. Aim: To assess dose-related effects of solabegron on gastrointestinal and colonic transit in healthy human volunteers. Methods: In a randomized, double-blind study, 37 healthy male and female volunteers were randomized to placebo, 50 mg or 200 mg solabegron every 12 hours for 7 days. They underwent questionnaires to exclude gastrointestinal symptoms and significant multiple somatic symptoms, scintigraphic gastrointestinal and colonic transit using a validated technique, and bowel function (including stool frequency and consistency measured by Bristol stool form scale). The primary endpoints for analysis were gastric emptying at 2 hours and colonic geometric center (GC) at 24 hours. Analysis of covariance [(ANCOVA), adjusting for gender and body mass index (BMI)], was followed by two pairwise comparisons of each solabegron dose compared to placebo.Results: There was no overall or dose-related effect of solabegron on gastric, small bowel or colonic transit, or on stool frequency, form or ease of passage in healthy volunteers (table). Conclusion: While further studies in patients with motility disorders are awaited, it does not appear that the β3-AR agonist, solabegron, significantly alters gastrointestinal or colonic motility in healthy volunteers.
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