Neurogastroenterology Group, Blizard Institute, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, 2 Newark Street, London, E1 2AT, UK.
Eur J Pharmacol. 2013 Sep 5;715(1-3):10-4. doi: 10.1016/j.ejphar.2013.06.031. Epub 2013 Jul 4.
Nausea is one of a cluster of symptoms described subjectively by patients with delayed gastric emptying. The mechanisms and treatments are unclear (anti-emetic drugs are not fully effective against nausea). Can nausea be relieved by stimulating gastric emptying? Physostigmine (together with atropine) has been shown experimentally to stimulate gastric motility, relieve nausea and restore normal gastric motility. Is this mimicked by gastric prokinetic drugs? The answer is complicated by mixed pharmacology. Metoclopramide increases gastric motility by activating myenteric 5-HT4 receptors but also directly inhibits vomiting via D2 and 5-HT3 receptor antagonism; relationships between increased gastric motility and relief from nausea are therefore unclear. Similarly, the D2 receptor antagonist domperidone has direct anti-emetic activity. Nevertheless, more selective 5-HT4 and motilin receptor agonists (erythromycin, directly stimulating gastric motility) inhibit vomiting in animals; low doses of erythromycin can also relieve symptoms in patients with gastroparesis. Ghrelin stimulates gastric motility and appetite mostly via vagus-dependent pathways, and inhibits vomiting in animals. To date, ghrelin receptor activation has failed to consistently improve gastric emptying or symptoms in patients with gastroparesis. We conclude that nausea can be relieved by gastric prokinetic drugs, but more clinical studies are needed using drugs with selective activity. Other mechanisms (e.g. ghrelin, vagal and central pathways, influencing a mechanistic continuum between appetite and nausea) also require exploration. These and other issues will be further explored in a forthcoming special issue of the European Journal of Pharmacology, which focusses on mechanisms of nausea and vomiting.
恶心是一组由胃排空延迟的患者主观描述的症状之一。其机制和治疗方法尚不清楚（止吐药对恶心不完全有效）。刺激胃排空能否缓解恶心？毒扁豆碱（与阿托品合用）已被实验证明可刺激胃动力，缓解恶心并恢复正常胃动力。胃动力药物是否能模拟这种作用？由于混合药理学的原因，答案变得复杂。甲氧氯普胺通过激活肠肌 5-HT4 受体来增加胃动力，但也通过 D2 和 5-HT3 受体拮抗作用直接抑制呕吐；因此，增加胃动力与缓解恶心之间的关系尚不清楚。同样，D2 受体拮抗剂多潘立酮具有直接的止吐作用。然而，更具选择性的 5-HT4 和胃动素受体激动剂（红霉素，直接刺激胃动力）可抑制动物呕吐；红霉素的低剂量也可缓解胃轻瘫患者的症状。胃饥饿素通过迷走神经依赖途径刺激胃动力和食欲，在动物中抑制呕吐。迄今为止，胃饥饿素受体激活未能一致改善胃轻瘫患者的胃排空或症状。我们的结论是，胃动力药物可以缓解恶心，但需要使用具有选择性活性的药物进行更多的临床研究。其他机制（例如，胃饥饿素、迷走神经和中枢途径，影响食欲和恶心之间的机制连续体）也需要探索。这些和其他问题将在即将出版的《欧洲药理学杂志》特刊中进一步探讨，该特刊重点关注恶心和呕吐的机制。
