The effect of erythromycin on human esophageal motility is mediated by serotonin receptors.

OBJECTIVE

Erythromycin exhibits prokinetic properties. The drug enhances esophageal and gastric motility by acting as a motilin agonist and promoting acetylocholine release. 5-HT3 receptors are involved in the spontaneously occurring migrating motor complex and the effect of erythromycin on antral motility in dogs. The aim of the study was to investigate the hypothesis that 5-HT3 receptors are also involved in the action of erythromycin on the human esophagus.

METHODS

A total of 18 healthy volunteers underwent standard esophageal manometry on three different occasions in a double-blind, placebo-controlled, randomized manner, as follows: 1) after placebo, 2) after 200 mg of erythromycin i.v., and 3) after 200 mg of i.v. erythromycin subsequent to pretreatment with either 4 mg of i. v. ondansetron (serotonin receptor antagonist) (10 subjects) or 12 microg/kg of i.v. atropine (8 subjects).

RESULTS

Erythromycin significantly increased a) the amplitude of peristalsis at 5 cm (from 87 +/- 19 mm Hg to 108 +/- 26 mm Hg; p = 0.0007), 10 cm (from 72 +/- 24 mm Hg to 81 +/- 26 mm Hg; p = 0.016), and 15 cm (from 47 +/- 15 mm Hg to 55 +/- 17 mm Hg; p = 0.014) proximal to LES, b) the duration of peristalsis at 5 cm (from 4.5 +/- 0.9 s to 5.7 +/- 1.2 s; p < 0.0001) and 10 cm (from 4.1 +/- 1 s to 4.9 +/- 1 s; p < 0.0001) proximal to the LES and c) the strength of peristalsis at 5 cm proximal to the LES (from 180 +/- 49 mm Hg x s to 276 +/- 100 mm Hg x s; p < 0.0001), and decreased the velocity of peristalsis at distal esophagus (from 4.1 +/- 1 cm/s to 3.8 +/- 0.9 cm/s; p = 0.03). In addition, erythromycin significantly increased the resting pressure of the LES (from 36 +/- 10 mm Hg to 44 +/- 12 mm Hg; p = 0.002). Pretreatment with ondansetron totally reversed all of the effects of erythromycin to the placebo state. Pretreatment with atropine not only prevented the effects of erythromycin, but it reduced the amplitude and strength of peristalsis at the distal esophagus at significantly lower levels than after placebo.

CONCLUSIONS

Erythromycin exerts its prokinetic action on the lower esophagus by stimulating cholinergic pathways. This action includes not only an increase in LES pressure, but significant increases in the amplitude and duration of esophageal peristalsis, as well. 5-HT3 receptors are also involved in this process.