title: Anti-emetic and emetic effects of erythromycin in Suncus murinus: role of vagal nerve activation, gastric motility stimulation and motilin receptors.
abstract: Paradoxically, erythromycin is associated with nausea when used as an antibiotic but at lower doses erythromycin activates motilin receptors and is used to treat delayed gastric emptying and nausea. The aim of this study was to characterise pro- and anti-emetic activity of erythromycin and investigate mechanisms of action. Japanese House musk shrews (Suncus murinus) were used. Erythromycin was administered alone or prior to induction of emesis with abnormal motion or subcutaneous nicotine (10mg/kg). The effects of erythromycin and motilin on vagal nerve activity and on cholinergically mediated contractions of the stomach (evoked by electrical field stimulation) were studied in vitro. The results showed that erythromycin (1 and 5mg/kg) reduced vomiting caused by abnormal motion (e.g., from 10.3 ± 1.8 to 4.0 ± 1.1 emetic episodes at 5mg/kg) or by nicotine (from 9.5 ± 2.0 to 3.1 ± 2.0 at 5mg/kg), increasing latency of onset to emesis; lower or higher doses had no effects. When administered alone, erythromycin 100mg/kg induced vomiting in two of four animals, whereas lower doses did not. In vitro, motilin (1, 100 nM) increased gastric vagal afferent activity without affecting jejunal afferent mesenteric nerve activity. Cholinergically mediated contractions of the stomach (prevented by tetrodotoxin 1 μM or atropine 1 μM, facilitated by l-NAME 300 μM) were facilitated by motilin (1-100 nM) and erythromycin (10-30 μM). In conclusion, low doses of erythromycin have anti-emetic activity. Potential mechanisms of action include increased gastric motility (overcoming gastric stasis) and/ or modulation of vagal nerve pathways involved in emesis, demonstrated by first-time direct recording of vagal activation by motilin.
authors.affiliation: School of Applied Sciences, Division of Pharmacy and Pharmaceuticals Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
authors.forename: Farideh A
authors.initials: FA
authors.lastname: Javid
authors.forename: David C
authors.initials: DC
authors.lastname: Bulmer
authors.forename: John
authors.initials: J
authors.lastname: Broad
authors.forename: Qasim
authors.initials: Q
authors.lastname: Aziz
authors.forename: George E
authors.initials: GE
authors.lastname: Dukes
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Sanger
mesh_terms: D000818:Animals; D000932:Antiemetics / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004917:Erythromycin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D009037:Motilin / Q000008:administration & dosage / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D012788:Shrews; D013270:Stomach / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism; D014839:Vomiting / Q000139:chemically induced / Q000188:drug therapy / Q000209:etiology
chemical_list: D000932:Antiemetics; D005765:Gastrointestinal Agents; D011964:Receptors, Gastrointestinal Hormone; D018013:Receptors, Neuropeptide; C050802:motilin receptor; D009037:Motilin; D004917:Erythromycin; D009538:Nicotine