The effects of lintopride, a 5HT-4 antagonist, on oesophageal motility

Aim : To evaluate the effects of various doses of lintopride, a new 5HT-4 antagonist with moderate SHT-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 (T 0 T 240 min). Results : The LOS basal pressure (23.3 ± 2.0 cmH 2 O ; mean ± s.d.) remained stable after dosing with placebo to T 240 . 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 T 30 after lintopride 0.3 mg/kg (34.5 cmH 2 O, P = 0.020) and 0.5 mg/kg (32.5 cmH 2 O, P = 0.027), at T 60 after 0.3 mg/kg (48.8 cmH 2 O, P = 0.0009) and 0.5 mg.kg (29.1 cmH 2 O, P = 0.029) and at T 90 after 0.3 mg/kg (34.5 cmH 2 O, 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.