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

OBJECTIVE: Erythromycin exhibits prokinetic properties. The drug enhances e sophageal 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 th at 5-HT3 receptors an also involved in the action of erythromycin on the hu man esophagus. METHODS: A total of 18 healthy volunteers underwent standard esophageal man ometry on three different occasions in a double-blind, placebo-controlled, randomized manner, as follows: 1) after placebo, 2) after 200 mg of erythro mycin i.v., and 3) after 200 mg of i.v. erythromycin subsequent to pretreat ment with either 4 mg of i.v. ondansetron (serotonin receptor antagonist) ( 10 subjects) or 12 mug/kg of i.v. atropine (8 subjects). RESULTS: Erythromycin significantly increased a) the amplitude of peristals is at 5 cm (from 87 +/- 19 mm Hg to 108 +/- 26 mm Hg; p = 0.0007), 10 cm (f rom 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 +/- 4 9 mm Hg.s to 276 +/- 100 mm Hg.s; p < 0.0001), and decreased the velocity o f 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 p ressure of the LES (from 36 +/- 10 mm Hg to 44 +/- 12 mm Hg; p = 0.002). Pr etreatment with ondansetron totally reversed all of the effects of erythrom ycin to the placebo state. Pretreatment with atropine not only prevented th e effects of erythromycin, but it reduced the amplitude and strength of per istalsis at the distal esophagus at significantly lower levels than after p lacebo. CONCLUSIONS: Erythromycin exerts its prokinetic action on the lower esophag us by stimulating cholinergic pathways. This action includes not only an in crease in LES pressure, but significant increases in the amplitude and dura tion of esophageal peristalsis, as well. 5-HT3 receptors are also involved in this process. (C) 2000 by Am. Cell. of Gastroenterology.