THE EFFECTS OF LINTOPRIDE, A 5HT-4 ANTAGONIST, ON ESOPHAGEAL MOTILITY

Aim: To evaluate the effects of Various doses of lintopride, a new 5HT -4 antagonist with moderate 5HT-3 antagonist properties, on oesophagea l body and lower oesophageal sphincter (LOS) motility in humans. Metho ds: Eight healthy male volunteers, mean age 22 (19-28) years, without any history of digestive disease or chest pain, were randomized to thr ee 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 motil ity 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 oeso phagus, at 5, 10 and 15 cm from the LOS. Peristalsis was studied durin g 10 wet swallows, at 30-min intervals (T-0-T-240 min). Results: The L OS basal pressure (23.3 +/- 2.0 cmH(2)O; mean +/- s.d.) remained stabl e after dosing with placebo to T-240. After lintopride, LOS basal pres sure increased significantly vs. placebo (AUG comparison: 0.1 mg/kg, P = 0.036; 0.3 mg/kg, P = 0.027; 0.5 mg/kg, P = 0.052). In contrast, th e duration and extent of LOS relaxation after swallowing was not affec ted by any of the three doses of lintopride. The amplitude of peristal tic waves in the oesophagus increased significantly at T-30 after lint opride 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 aft er swallowing. Peristaltic waves were also enhanced by lintopride.