Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers.
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.


OBJECTIVE
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.
Clemens
C H M
CH
Gastrointestinal Research Unit, Departments of Gastroenterology and Surgery, University Medical Center Utrecht, The Netherlands.
Samsom
M
M
Van Berge Henegouwen
G P
GP
Fabri
M
M
Smout
A J P M
AJ
D000328:Adult; D002243:Carbolines / Q000009:adverse effects / Q000627:therapeutic use*; D003106:Colon / Q000187:drug effects; D003109:Colonic Diseases, Functional / Q000188:drug therapy*; D018592:Cross-Over Studies; D003672:Defecation / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D008297:Male; D008365:Manometry; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron