Department of Pharmacy, Faculty of Sciences, University of Swabi, Anbar, Swabi, 23430, Khyber Pakhtunkhwa, Pakistan.
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
Pharmacol Rep. 2023 Oct;75(5):1126-1137. doi: 10.1007/s43440-023-00514-z. Epub 2023 Aug 16.
The neural mechanisms and the receptors behind the course of chemotherapy-induced nausea and vomiting (CINV) are well described and considered mechanistically multifactorial, whereas the neurobiology of nausea is not completely understood yet. Some of the anti-neoplastic medications like cisplatin result in biphasic vomiting response. The acute phase of vomiting is triggered mainly via the release of serotonin from the enterochromaffin (EC) cells in the gastrointestinal tract (GIT) and results in stimulation of dorsal vagal complex (DVC) of the vomiting center and the vomiting is initiated by downward communication to the gut via vagal efferents. Agonism of 5HT receptors is majorly involved in the mediation of the acute phase. Therefore, antagonists at 5HT receptors are effective in the management of acute-phase vomiting episodes. Likewise, Dopamine type 2 (D) receptors, dopamine neurotransmitter, Muscarinic receptors (M), GLP receptors, and histaminergic receptors (H) are also implicated in the vomiting act as well. In continuation, Cannabinoid type 1 (CB) receptors are also recommended and included in the guidelines as agonism of presynaptically located CB receptors inhibits the release of excitatory neurotransmitters responsible for vomiting initiation. The delayed phase involves the release of "Substance P" in the gut and results in the stimulation of neurokinin-1 (NK) receptors centrally in the area postrema (AP) and nucleus tractus solitarius (NTS), subsequently the vomiting response. The current understanding is the existence of overlapping mechanisms of neurotransmitters, serotonin, dopamine, and substance P throughout the time course of CINV. Furthermore, the emetic neurotransmitters are released via calcium ion (Ca)-dependent mechanisms, implicating the molecular targets of intracellular Ca signaling in emetic circuitry. The current review entails the neurobiology of nausea and vomiting induced by cancer chemotherapeutic agents and the recent approaches in the management.
化疗引起的恶心和呕吐（CINV）的神经机制和受体已经得到了很好的描述，并被认为是机械性多因素的，而恶心的神经生物学尚未完全理解。一些抗肿瘤药物，如顺铂，会导致双相呕吐反应。呕吐的急性期主要是通过胃肠道（GIT）中的肠嗜铬细胞（EC）细胞释放 5-羟色胺（5-HT）而引发的，这导致了呕吐中枢的背侧迷走复合体（DVC）的刺激，并且通过迷走神经传出纤维向下传递到肠道来引发呕吐。5-HT 受体激动剂主要参与了急性期的介导。因此，5-HT 受体拮抗剂在急性呕吐发作的管理中是有效的。同样，多巴胺 2 型（D）受体、多巴胺神经递质、毒蕈碱受体（M）、GLP 受体和组氨酸能受体（H）也参与了呕吐作用。此外，大麻素 1 型（CB）受体也被推荐并包含在指南中，因为位于突触前的 CB 受体的激动剂抑制了负责呕吐起始的兴奋性神经递质的释放。迟发性阶段涉及到“P 物质”在肠道中的释放，导致神经激肽-1（NK）受体在延髓后极（AP）和孤束核（NTS）中的中枢刺激，随后出现呕吐反应。目前的理解是，在 CINV 的整个时间过程中，神经递质、5-HT、多巴胺和 P 物质的存在重叠机制。此外，呕吐递质通过钙离子（Ca）依赖性机制释放，这意味着细胞内 Ca 信号转导的分子靶点在呕吐回路中。本综述涉及到癌症化疗药物引起的恶心和呕吐的神经生物学以及最近的管理方法。
