Motilin agonist erythromycin increases human lower esophageal sphincter pressure by stimulation of cholinergic nerves

Abstract

During phases II and III of the migrating motor complex, there is an increase in plasma motilin level that is synchronous with phasic and tonic contractile activity of the lower esophageal sphincter and of the stomach. The action of motilin on human lower esophageal sphincter is proposed to be mediated by cholinergic mechanisms. Recently, it has been shown that erythromycin was a motilin agonist. This study evaluated the pharmacological effects and the mechanism of action of intravenous erythromycin on esophageal motility in humans. Healthy volunteers were studied three times at seven-day intervals in a randomized, double-blind fashion. Subjects were first studied for 10 min before drug administration. Afterwards, they received blindly and randomly an intravenous injection of placebo or atropine (12 µg/kg) followed by a 20-min continuous intravenous administration of placebo or erythromycin (150 mg). The difference (Δ) between lower esophageal sphincter pressure and the duration, amplitude, and velocity of peristaltic contractions during the control period and after administration of drugs was compared. Erythromycin significantly increased (P<0.05) the lower esophageal sphincter pressure (16.8 ± 4.7 mm Hg) compared to placebo (−0.029 ± 1.4 mm Hg). Erythromycin significantly decreased peristaltic contraction velocity compared to placebo (P<0.05). The effects of erythromycin on lower esophageal sphincter pressure were completely blocked by previous administration of intravenous atropine. Erythromycin increased the number of fundic contractions compared to the placebo, but this effect was not blocked by the previous administration of atropine. Based on these observations, it is proposed that the motilin agonist erythromycin acts on the lower esophageal sphincter by stimulating cholinergic nerves but also could modify gastric motility by direct muscle stimulation.