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

Aims 5-hydroxytryptamine(3) receptor antagonists act antiemetically and slo w 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 thre e 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 c m h-om 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 th e 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 neo stigmine was administered intramuscularly and motility recording was contin ued for 60 min Results Phasic contractile activity and intraluminal base-line pressure inc reased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the numbe r of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not aff ected. The effects of the two cilansetron dosages did not differ. With cila nsetron, stool tended to become firmer. No adverse effects were observed. P lasma levels were highest with 8 mg cilansetron. Conclusions Cilansetron slightly augments meal-stimulated and markedly neos tigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.