Involvement of two diVerent pathways in the motor eVects of erythromycin on the gastric antrum in humans

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 themotor eVects 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 stationarymanometry. Placebo (n=10), atropine (15 μg/kg intravenous bolus plus 15 μg/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 diVer significantly after atropine or sumatriptan versus placebo. Conclusions—The antral motor eVects of erythromycin in humans are mediated via diVerent 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. (Gut 1998;43:395–400)