Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome.
BACKGROUND
Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and improves bowel function in non-constipated, female patients with irritable bowel syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption.


OBJECTIVE
To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome.


METHODS
A double-blind, placebo-controlled, two-dose study of alosetron was performed in 25 non-constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat.


RESULTS
There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo.


CONCLUSIONS
Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non-constipated irritable bowel syndrome patients in this study. Alosetron's effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.
Thumshirn
M
M
Gastroenterology Research Unit, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Coulie
B
B
Camilleri
M
M
Zinsmeister
A R
AR
Burton
D D
DD
Van Dyke
C
C
D000328:Adult; D000368:Aged; D002243:Carbolines / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003109:Colonic Diseases, Functional / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011597:Psychomotor Performance / Q000187:drug effects; D012007:Rectum / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use
D002243:Carbolines; D012702:Serotonin Antagonists; C090840:alosetron