Tegaserod, a 5-HT4 receptor partial agonist, accelerates gastric emptying and gastrointestinal transit in healthy male subjects.
BACKGROUND
Serotonin and its type-4 (5-hydroxytryptamine4) receptor play a major role in the physiology of the gastrointestinal tract. The effect of intravenous and/or oral tegaserod, a 5-hydroxytryptamine4 receptor partial agonist, on gastric emptying, small bowel transit and colonic transit has not been studied in detail in humans.


OBJECTIVE
To assess the pharmacodynamic effects of repeated oral and intravenous administration of tegaserod on gastric emptying and small intestine and colonic transit.


METHODS
A randomized, placebo-controlled, double-blind, three-way, crossover study of 6 mg oral and 0.6 mg intravenous tegaserod in 12 healthy male subjects was performed. Each treatment arm of the study involved 3 days of twice-daily administration and 1 day of daily administration of the study drugs.


RESULTS
In comparison with placebo, oral and intravenous tegaserod significantly increased the gastric emptying rate (P < 0.01), accelerated colonic filling (P < 0.01) and shortened colonic transit at 48 h (P < 0.05). Tegaserod shortened the small intestine transit time by 30% after oral and by 37% after intravenous administration.


CONCLUSIONS
In healthy subjects, tegaserod markedly accelerated gastric emptying and small intestinal transit, and induced a small but significant acceleration of colonic transit. Tegaserod can act as a promotile agent throughout the gastrointestinal tract.
Degen
L
L
Division of Gastroenterology, University Hospital, Basel, Switzerland.
Matzinger
D
D
Merz
M
M
Appel-Dingemanse
S
S
Osborne
S
S
Lüchinger
S
S
Bertold
R
R
Maecke
H
H
Beglinger
C
C
D000284:Administration, Oral; D000328:Adult; D003106:Colon / Q000187:drug effects / Q000502:physiology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005746:Gastric Emptying / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D007211:Indoles; D017366:Serotonin Receptor Agonists; C105050:tegaserod