The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility.
OBJECTIVE
To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate 5HT-3 antagonist properties, on oesophageal body and lower oesophageal sphincter (LOS) motility in humans.


METHODS
Eight healthy male volunteers, mean age 22 (19-28) years, without any history of digestive disease or chest pain, were randomized to three doses of lintopride (0.1, 0.3 and 0.5 mg/kg i.v.) and a placebo at 1-week intervals in a double-blind, crossover study. Oesophageal motility was recorded continuously for 4 h after each dose, using perfused catheters inserted at the level of the LOS and in the body of the oesophagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (T0-T240 min).


RESULTS
The LOS basal pressure (23.3 +/- 2.0 cmH2O; mean +/- s.d.) remained stable after dosing with placebo to T240. After lintopride, LOS basal pressure increased significantly vs. placebo (AUC comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P = 0.052). In contrast, the duration and extent of LOS relaxation after swallowing was not affected by any of the three doses of lintopride. The amplitude of peristaltic waves in the oesophagus increased significantly at T30 after lintopride 0.3 mg/kg (34.5 cmH2O, P = 0.020) and 0.5 mg/kg (32.5 cmH2O, P = 0.027), at T60 after 0.3 mg/kg (48.8 cmH2O, P = 0.0009) and 0.5 mg/kg (29.1 cmH2O, P = 0.029) and at T90 after 0.3 mg/kg (34.5 cmH2O, P = 0.0018).


CONCLUSIONS
Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. Peristaltic waves were also enhanced by lintopride.
Delvaux
M
M
Gastroenterology Unit, Centre Hospitalier Universitaire Rangueil, Toulouse, France.
Maisin
J M
JM
Arany
Y
Y
Atlan
P
P
Prieto-Cabanis
M J
MJ
Canal
M
M
Frexinos
J
J
D000328:Adult; D004943:Esophagogastric Junction / Q000187:drug effects; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010528:Peristalsis / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects*; D044422:Receptors, Serotonin, 5-HT4; D012016:Reference Values
D007093:Imidazoles; D011985:Receptors, Serotonin; D044422:Receptors, Serotonin, 5-HT4; C065607:lintopride