FAILURE OF TROPISETRON TO INHIBIT JEJUNAL WATER AND ELECTROLYTE SECRETION INDUCED BY 5-HYDROXYTRYPTAMINE IN HEALTHY-VOLUNTEERS

The effects of the 5-hydroxytryptamine (5-HT3) receptor antagonist, IC S 205-930 (tropisetron), on basal and 5-HT induced jejunal secretion o f water and electrolytes were examined using a double blind, randomise d crossover design. In seven healthy volunteers steady state perfusion s of the proximal jejunum were performed twice with the Loc-I-Gut tube after 5+5 mg ICS 205-930 or placebo capsules were given. After equili bration for 60 minutes and completion of a 120 minute basal period 5-H T (10 mu g/kg X min intravenously) was infused for 120 minutes. Net wa ter absorption (mean (SEM)) in the basal period was 0.55 (0.84) ml/cm X h and 0.74 (0.72) ml/cm X h after placebo and ICS 205-930, respectiv ely (p>0.05), Infusion of 5-HT caused significant net secretion of wat er after placebo (2.05 (0.58) ml/cm X h; p<0.02) as well as ICS 205-93 0 (2.60 (0.89) ml/cm X h; p<0.05). As ICS 205-930 excerted no effects on either basal or 5-HT induced water and electrolyte transport in the intact human jejunum the compound is probably not efficacious as an a nti-secretory drug in patients with 5-HT induced diarrhoea.