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

Abstract

S U M M A R YAim : 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 (1 9-2 8) 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 1 5 cm from the LOS. Peristalsis was studied during 10 wet swallows, at 30-min intervals (&-q4, min). Results: The LOS basal pressure (2 3.3 _+ 2 .O cmH,O ; mean k s.d.) remained stable after dosing with placebo to TA4,. 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 I j , after lintopride 0.3 mg/kg (34.5 cmH,O, P = 0.020) and 0.5 mg/kg (32.5 cmH,O, P = 0.027), at Go after 0.3 mg/kg (48.8 cmH,O, P = 0.0009) and 0.5 mg.kg (29.1 cmH,O, P = 0.029) and at T,, after 0.3 mg/kg (34.5 cmH,O, P = 0.0018). Conclusions : Lintopride significantly increased the LOS basal tone without affecting LOS physiological relaxation after swallowing. PeristaItic waves were also enhanced by lintopride. 0 19Y 5 Blackwell Science Ltd 563

Effect of citalopram on esophageal motility in healthy subjects—Implications for reflux episodes, dysphagia, and globus

“…The increase in LES tone after administration of the SSRI citalopram did not come as a surprise, as earlier studies have linked drugs acting on 5HT‐receptors with higher LES pressure values . In our study, although the ability of the LES to relax was maintained, citalopram infusion led to higher LES resting pressures extending from the preprandial period until the first postprandial hour.…”

“…The increase in LES tone after administration of the SSRI citalopram did not come as a surprise, as earlier studies have linked drugs acting on 5HT-receptors with higher LES pressure values. [24][25][26][27] In our study, although the ability of the LES to relax was maintained, citalopram infusion led to higher LES resting pressures extending from the preprandial period until the first postprandial hour. In that concept, it would be reasonable to assume that the TLESRs should mostly occur during the second instead of the first postprandial hour since this is when LES pressures between citalopram and placebo were not different.…”

“…Cisapride, a 5HT 4 receptor agonist, originally used for GERD and gastroparesis, enhances LES pressure. Lintopride, a 5HT 3 /5HT 4 receptor agonist, can increase LES basal tone and amplify esophageal peristalsis . Furthermore, buspirone, a 5HT 1A receptor agonist, can increase LES pressure and esophageal peristaltic vigor .…”

“…Lintopride, a 5HT 3 /5HT 4 receptor agonist, can increase LES basal tone and amplify esophageal peristalsis. [24][25][26] Furthermore, buspirone, a 5HT 1A receptor agonist, can increase LES pressure and esophageal peristaltic vigor. 27 On the other hand, sumatriptan, a 5HT 1B /5HT 1D receptor agonist, increases the frequency of postprandial TLESRs and reflux, despite an increase in postprandial LES pressure.…”

Beneficial effect of the 5‐HT1A receptor agonist buspirone on esophageal dysfunction associated with systemic sclerosis: A pilot study

“…22 Several studies have evaluated the effects of 5-HT 4 agonists on esophageal peristalsis and LES function in non-SSc patients, showing different results. [23][24][25][26][27] However, use of these agents is restricted due to cardiac safety profile issues. Another serotonin receptor agonist, namely the 5-HT1A receptor agonist sumatriptan, may enhance esophageal peristalsis after subcutaneous administration in healthy subjects.…”