Effect of atilmotin, a motilin receptor agonist, on esophageal, lower esophageal sphincter, and gastric pressures

Abstract

Background: Motilin, an endogenous gastrointestinal (GI) hormone, increases upper gastrointestinal tract motility and is associated with phase III of the gastric migrating motor complex. The motilin receptor agonist, atilmotin, at doses of 6, 30 or 60 microg intravenously (IV), increases the early phase of gastric emptying. Prior studies at higher doses of 100-450 microg IV demonstrated that some subjects developed noncardiac chest pain.

Aims: The aim of this study is to determine the effects of atilmotin on esophageal, lower esophageal sphincter (LES), and gastric contractility and the development of esophageal-related symptoms.

Methods: Ten healthy volunteers underwent esophageal manometry to study the effects of atilmotin on upper GI motility. Five subjects were studied on three separate days following administration of saline placebo and subsequent IV bolus dose of atilmotin (6, 30 or 150 microg). Another five subjects were studied at the highest dose (150 microg).

Results: Atilmotin at 150 microg increased proximal gastric pressure by 6.5 mmHg (P = 0.001 compared with placebo). Atilmotin increased LES pressure at all studied doses; LES pressure increased from 24 +/- 2 mmHg following placebo injection to 34 +/- 4 mmHg following a 30 microg dose of atilmotin (P = 0.007). In the esophagus, atilmotin increased the percentage of failed swallows at the highest dose studied. Failed swallows increased from 17 +/- 7% following placebo injection to 36 +/- 7% following a 150 microg dose of atilmotin (P = 0.016). Atilmotin decreased distal esophageal contractile amplitude only at the highest dose studied, from 69 +/- 8 mmHg (placebo) to 50 +/- 5 mmHg following 150 microg atilmotin (P = 0.018). There were no serious adverse effects or episodes of chest pain with atilmotin.

Conclusions: Atilmotin affects esophageal, LES, and gastric motility. LES and gastric pressures were increased, whereas there was disruption of esophageal peristalsis characterized by lower amplitude and failed contractions.

Fig. 1

Esophageal manometry tracings illustrating the effect of atilmotin: a after placebo (saline infusion) and b after atilmotin. In each figure, the top tracing is the high-resolution contour mapping and the bottom tracing is the conventional esophageal manometry tracing. In the high-resolution contour mapping, the catheter traverses the entire esophagus from the upper esophageal sphincter at top to the lower esophageal sphincter at the bottom. The amplitude scale is shown at the left. Esophageal peristalsis after swallowing is indicated by the contour peak traversing down and to the right. a Normal subject after saline injection, b normal subject after atilmotin IV

Fig. 1

Esophageal manometry tracings illustrating the effect of atilmotin: a after placebo (saline infusion) and b after atilmotin. In each figure, the top tracing is the high-resolution contour mapping and the bottom tracing is the conventional esophageal manometry tracing. In the high-resolution contour mapping, the catheter traverses the entire esophagus from the upper esophageal sphincter at top to the lower esophageal sphincter at the bottom. The amplitude scale is shown at the left. Esophageal peristalsis after swallowing is indicated by the contour peak traversing down and to the right. a Normal subject after saline injection, b normal subject after atilmotin IV

Fig. 2

Change in LES pressure over time after atilmotin infusion. Shown is the LES pressure in mmHg (y axis) and the swallow number after 6 µg atilmotin intravenously (squares) and after saline injection (diamonds). There was an increase in LES pressure seen after the first five swallows after atilmotin infusion; thereafter there were similar values to placebo. Shown are the mean values of LES pressure relative to gastric pressure for five subjects