组胺与恶心呕吐机制：解读赛克利嗪不确定的药理学

文献信息

中文摘要

赛克利嗪是一种历史悠久的短效药物，注册用于预防晕动病、术后恶心呕吐（PONV）和“已知原因的呕吐”。后者未明确定义，但可能包括妊娠和接受姑息治疗的患者，历史上在没有大型对照试验的情况下被接受。赛克利嗪常被描述为“抗组胺药”，有时也被称为“抗胆碱能药”，但未引用原始文献。其止吐活性的机制了解甚少。我们回顾了赛克利嗪已发表的药理学，旨在了解其止吐活性的机制。检查了临床前/临床研究，并参考已知的恶心呕吐机制对发现进行了解释。赛克利嗪拮抗人H1受体，可能引起轻度嗜睡。作用选择性尚不清楚；治疗剂量仅微弱拮抗毒蕈碱型乙酰胆碱受体。晕动病通过前庭系统及相关脑干核团内的H1拮抗得到改善。组胺可能参与PONV的机制尚不清楚。也许来自肥大细胞和嗜碱性粒细胞的组胺刺激/敏化腹部迷走传入神经，与其他物质协同引起呕吐。妊娠期间赛克利嗪对呕吐的任何抑制作用尚不清楚；GDF15被牵涉其中，但与组胺的关系不明确。姑息治疗期间恶心/呕吐的原因可能很复杂，赛克利嗪的使用并不了解其机制。对于所有适应症，尚不清楚恶心是否以与呕吐相同的程度减轻。没有一致的证据支持使用赛克利嗪治疗胃轻瘫或放化疗期间的呕吐。赛克利嗪的药理学及其止吐活性机制了解甚少。提出了可检验的假设。

英文摘要

Cyclizine is a long-established, short-acting drug, registered for preventing motion sickness, post-operative nausea and vomiting (PONV) and 'vomiting of known cause'. The latter is not defined but may include pregnancy and patients receiving palliative care, historically accepted without large, controlled trials. Cyclizine is often described as an 'antihistamine' and sometimes 'anticholinergic', without citing primary literature. Mechanisms of antiemetic activity are poorly understood. We reviewed the published pharmacology of cyclizine with the aim of understanding its mechanism of antiemetic activity. Preclinical/clinical studies were examined and findings interpreted with reference to known mechanisms of nausea and vomiting. Cyclizine antagonizes human H1 receptors and may cause mild drowsiness. Selectivity of action is unclear; therapeutic doses only weakly antagonize muscarinic ACh receptor(s). Motion sickness is ameliorated by H1 antagonism within the vestibular system and associated brainstem nuclei. Mechanisms by which histamine may contribute to PONV are unclear. Perhaps histamine from mast cells and basophils stimulate/sensitize abdominal vagal afferent nerves, synergising with other substances to cause vomiting. Any inhibition of vomiting by cyclizine during pregnancy is not understood; GDF15 is implicated, but relationships with histamine are unclear. Causes of nausea/vomiting during palliative care can be complex, and cyclizine is used without understanding mechanisms. For all indications, it is unclear if nausea is reduced to the same degree as vomiting. There is no consistent evidence to support using cyclizine for vomiting during gastroparesis or chemoradiotherapy. The pharmacology of cyclizine and mechanisms of its antiemetic activity are poorly understood. Testable hypotheses are suggested.