TY - JOUR
T1 - 5-HT4 receptor antagonism in irritable bowel syndrome
T2 - Effect of SB-207266-A on rectal sensitivity and small bowel transit
AU - Houghton, L. A.
AU - Jackson, N. A.
AU - Whorwell, P. J.
AU - Cooper, S. M.
PY - 1999
Y1 - 1999
N2 - Background: Pre-clinical studies indicate that the 5-hydroxytryptamine (5-HT)4 receptor may be involved in the pathophysiology of irritable bowel syndrome and that antagonism of this receptor may be an effective therapeutic strategy. Aim: To investigate the effects of SB-207266-A, a selective 5-HT4 receptor antagonist on rectal sensitivity and small bowel transit in patients with irritable bowel syndrome. Methods: Eighteen patients with diarrhoea-predominant irritable bowel syndrome and a history of increased rectal sensitivity were randomized to receive either SB-207266-A (20 mg) or placebo for 10 days. Following a washout period, patients were then crossed over to receive the alternative therapy for 10 days. Rectal sensitivity and orocaecal transit time were assessed on day 10 of each treatment period. In addition, patients were asked whether they had experienced any changes in their symptoms. Results: Fifteen patients completed the study. SB-207266-A significantly increased orocaecal transit time towards normal (placebo: 5.3 h (4.0-7.2 h), mean (IQR) vs. SB-207266-A: 6.5 h (4.8-8.0 h); P = 0.027) and tended to decrease rectal sensitivity (volume to discomfort 89 mL (60-150 mL), geometric mean (IQR) vs. 107 mL (75-150 mL); P = 0.134). Eleven out of 15 patients reported symptomatic improvements with SB-207266-A but none with placebo. SB-207266-A was well tolerated. Conclusion: Our results support a role for the 5-HT4 receptor in the pathophysiology of irritable bowel syndrome and suggest that the selective 5-HT4 antagonist, SB-207266-A, is worthy of further evaluation in this disorder.
AB - Background: Pre-clinical studies indicate that the 5-hydroxytryptamine (5-HT)4 receptor may be involved in the pathophysiology of irritable bowel syndrome and that antagonism of this receptor may be an effective therapeutic strategy. Aim: To investigate the effects of SB-207266-A, a selective 5-HT4 receptor antagonist on rectal sensitivity and small bowel transit in patients with irritable bowel syndrome. Methods: Eighteen patients with diarrhoea-predominant irritable bowel syndrome and a history of increased rectal sensitivity were randomized to receive either SB-207266-A (20 mg) or placebo for 10 days. Following a washout period, patients were then crossed over to receive the alternative therapy for 10 days. Rectal sensitivity and orocaecal transit time were assessed on day 10 of each treatment period. In addition, patients were asked whether they had experienced any changes in their symptoms. Results: Fifteen patients completed the study. SB-207266-A significantly increased orocaecal transit time towards normal (placebo: 5.3 h (4.0-7.2 h), mean (IQR) vs. SB-207266-A: 6.5 h (4.8-8.0 h); P = 0.027) and tended to decrease rectal sensitivity (volume to discomfort 89 mL (60-150 mL), geometric mean (IQR) vs. 107 mL (75-150 mL); P = 0.134). Eleven out of 15 patients reported symptomatic improvements with SB-207266-A but none with placebo. SB-207266-A was well tolerated. Conclusion: Our results support a role for the 5-HT4 receptor in the pathophysiology of irritable bowel syndrome and suggest that the selective 5-HT4 antagonist, SB-207266-A, is worthy of further evaluation in this disorder.
UR - http://www.scopus.com/inward/record.url?scp=0032589965&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032589965&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2036.1999.00625.x
DO - 10.1046/j.1365-2036.1999.00625.x
M3 - Article
C2 - 10571599
AN - SCOPUS:0032589965
SN - 0269-2813
VL - 13
SP - 1437
EP - 1444
JO - Alimentary Pharmacology and Therapeutics
JF - Alimentary Pharmacology and Therapeutics
IS - 11
ER -