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, ICS 205-930 (tropisetron), on basal and 5-HT induced jejunal secretion of water and electrolytes were examined using a double blind, randomised crossover design. In seven healthy volunteers steady state perfusions 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 equilibration for 60 minutes and completion of a 120 minute basal period 5-HT (10 micrograms/kg x min intravenously) was infused for 120 minutes. Net water 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, respectively (p > 0.05). Infusion of 5-HT caused significant net secretion of water after placebo (2.05 (0.58) ml/cm x h; p < 0.02) as well as ICS 205-930 (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 anti-secretory drug in patients with 5-HT induced diarrhoea.
Munck
L K
LK
Department of Medical Gastroenterology, Hvidovre Hospital, University of Copenhagen, Denmark.
Eskerod
O
O
Hansen
M B
MB
Bukhave
K
K
Rask-Madsen
J
J
D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D004311:Double-Blind Method; D004573:Electrolytes / Q000378:metabolism*; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010477:Perfusion; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077526:Tropisetron
D004573:Electrolytes; D007211:Indoles; D012702:Serotonin Antagonists; D012701:Serotonin; D000077526:Tropisetron