Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans

Abstract

Background: During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity.

Aims: To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan.

Methods: In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg.

Results: After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo.

Conclusions: The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.

Figure 1

Effect of atropine and sumatriptan on the initiation of an antral activity front by erythromycin 40 mg intravenously in a healthy volunteer. All traces begin at the start of the infusion of erythromycin, which lasted 10 minutes. (A) Erythromycin caused a premature activity front at the antral level that migrated caudally to the small intestine. (B) Prior administration of atropine blocked the generation of a premature activity front by erythromycin during a 60 minute period. (C) Prior administration of sumatriptan also blocked the generation of a premature activity front by erythromycin during a 60 minute period.

Figure 2

Effect of atropine and sumatriptan on antral contractile activity induced by erythromycin 200 mg intravenously in a healthy volunteer. All traces begin at the start of the infusion of erythromycin, which lasted 10 minutes. (A) Erythromycin caused a burst of prolonged contractile activity at the antral level that did not migrate to the small intestine and was not followed by a phase 1. (B) Prior administration of atropine did not influence the occurrence of this prolonged antral contractile activity. (C) Prior administration of sumatriptan also did not block the erythromycin induced prolonged antral contractile activity.