School of Applied Sciences, Division of Pharmacy and Pharmaceuticals Sciences, University of Huddersfield, Queensgate, Huddersfield HD1 3DH, UK.
Eur J Pharmacol. 2013 Jan 15;699(1-3):48-54. doi: 10.1016/j.ejphar.2012.11.035. Epub 2012 Nov 28.
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.
矛盾的是，红霉素作为抗生素使用时会引起恶心，但低剂量的红霉素会激活胃动素受体，用于治疗胃排空延迟和恶心。本研究旨在描述红霉素的止吐和催吐活性，并研究其作用机制。使用日本鼩鼱（Suncus murinus）。单独给予红霉素或在异常运动或皮下尼古丁（10mg/kg）诱导呕吐之前给予红霉素。研究了红霉素和胃动素对迷走神经活动以及电刺激诱发的胃（胆碱能介导的收缩）的影响。结果表明，红霉素（1 和 5mg/kg）减少了由异常运动（例如，5mg/kg 时从 10.3 ± 1.8 到 4.0 ± 1.1 呕吐发作）或尼古丁（从 9.5 ± 2.0 到 3.1 ± 2.0）引起的呕吐，增加了呕吐发作的潜伏期；较低或较高剂量则没有影响。单独给予时，红霉素 100mg/kg 引起 4 只动物中的 2 只呕吐，而较低剂量则没有。在体外，胃动素（1、100nM）增加了胃迷走传入活动，而不影响空肠传入肠系膜神经活动。胃的胆碱能介导的收缩（1μM 河豚毒素或 1μM 阿托品阻断，300μM l-NAME 促进）被胃动素（1-100nM）和红霉素（10-30μM）促进。结论：低剂量的红霉素具有止吐活性。潜在的作用机制包括增加胃动力（克服胃排空延迟）和/或调节参与呕吐的迷走神经通路，这是通过胃动素首次直接记录迷走神经激活来证明的。
