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Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.

Abstract：

AIMS:5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS:Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS:Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS:Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.

journal_name

Br J Clin Pharmacol

journal_title

British journal of clinical pharmacology

authors

Stacher G,Weber U,Stacher-Janotta G,Bauer P,Huber K,Holzäpfel A,Krause G,Steinborn C

doi

10.1046/j.1365-2125.2000.00180.x

keywords:

subject

Has Abstract

pub_date

2000-05-01 00:00:00

pages

429-36

issue

eissn

0306-5251

issn

1365-2125

pii

bcp180

journal_volume

pub_type

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Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.