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Background: Alosetron is a 5-hydroxytryptamine-3 receptor antagonist reducing symptoms in female patients with diarrhoea-predominant irritable bowel syndrome, and is known to increase the colonic transit time. Aim: To study the effect of alosetron on left colonic phasic motility in ambulant non-constipated patients with irritable bowel syndrome and healthy volunteers. Methods: In a double-blind, randomized, crossover design, 10 patients with irritable bowel syndrome and 12 sex- and age-matched volunteers were treated for two 7-day periods with alosetron, 4 mg b.d., or placebo b.d. On day 6 of each treatment period, a six-channel solid-state manometric catheter was positioned in the left colon and 24 h motility was studied on day 7. The periprandial phasic motility around dinnertime was evaluated in the descending and sigmoid colon. The high-amplitude propagated contraction frequency and characteristics were calculated. Results: Alosetron appeared to increase the overall periprandial frequency in the sigmoid colon (P =0.043) and the mean amplitude of colonic contractions in the descending colon (P =0.007). The high-amplitude propagated contraction frequency was higher on alosetron during the second half of the day for patients with irritable bowel syndrome (P =0.002), with increased mean propagation length of high-amplitude propagated contractions (P =0.001). The stool frequency (P =0.024) and stool consistency score (P =0.002) were decreased by alosetron. Conclusions: The 5-hydroxytryptamine-3 receptor antagonist alosetron marginally increased left colonic periprandial phasic motility. Alosetron increased the number and propagation length of high-amplitude propagated contractions, which were paradoxically accompanied by a decrease in stool frequency and a firming of stool consistency. [ABSTRACT FROM AUTHOR]