Dopamine receptors in emesis: Molecular mechanisms and potential therapeutic function.
Dopamine receptors in emesis: Molecular mechanisms and potential therapeutic function.
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DOI：
10.1016/j.phrs.2020.105124
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发表时间：
2020-11
影响因子：
9.3
通讯作者：
Darmani NA
中科院分区：
文献类型：
--
作者：
Belkacemi L;Darmani NA
多巴胺是儿茶酚胺家族的一员，与多种生理功能有关。多巴胺及其五种受体亚型与精神分裂症、帕金森氏症、抑郁症、注意力缺陷多动症和不宁腿综合征等神经系统疾病密切相关。不幸的是，一些用于治疗这些疾病的基于多巴胺受体的激动剂会引起恶心和呕吐，这是即将发生的副作用。多巴胺受体配体与许多其他靶点（包括g蛋白偶联受体、转运体、酶和离子通道）的高度交叉相互作用，增加了发现治疗恶心和呕吐新靶点的复杂性。利用信号级联的激活状态作为基于机制的生物标志物来预测药物敏感性，结合基于多巴胺受体的偏倚激动剂的开发，可能会有很大的前景，似乎是治疗此类多因素疾病的药物开发的下一步。在这篇综述中，我们更新了目前关于多巴胺和多巴胺受体及其在恶心和呕吐中的潜在作用的知识。本综述提供的前期和临床证据支持多巴胺和多巴胺受体激动剂对呕吐发生率的影响。除了传统的多巴胺能止吐药物外，潜在的新型止吐药物靶向吐蛋白信号级联可能具有优越的选择性和效力。
Dopamine is a member of the catecholamine family and is associated with multiple physiological functions. Together with its five receptor subtypes, dopamine is closely linked to neurological disorders such as schizophrenia, Parkinson’s disease, depression, attention deficit–hyperactivity, and restless leg syndrome. Unfortunately, several dopamine receptor-based agonists used to treat some of these diseases cause nausea and vomiting as impending side-effects. The high degree of cross interactions of dopamine receptor ligands with many other targets including G-protein coupled receptors, transporters, enzymes, and ion-channels, add to the complexity of discovering new targets for the treatment of nausea and vomiting. Using activation status of signaling cascades as mechanism-based biomarkers to foresee drug sensitivity combined with the development of dopamine receptor-based biased agonists may hold great promise and seems as the next step in drug development for the treatment of such multifactorial diseases. In this review, we update the present knowledge on dopamine and dopamine receptors and their potential roles in nausea and vomiting. The pre- and clinical evidence provided in this review supports the implication of both dopamine and dopamine receptor agonists in the incidence of emesis. Besides the conventional dopaminergic antiemetic drugs, potential novel antiemetic targeting emetic protein signaling cascades may offer superior selectivity profile and potency.
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DOI：
10.1073/pnas.96.22.12866
发表时间：
1999-10-26
影响因子：
11.1
作者：
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DOI：
10.1073/pnas.0307921101
发表时间：
2004-04-06
影响因子：
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作者：
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