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[摘要]
多巴胺D3受体(D3R)是一种G蛋白偶联的D2样受体,多表达于与认知、情绪等脑机能密切相关的边缘区域。以D3R为靶标治疗帕金森病、精神分裂症及药物成瘾等中枢神经系统疾病具有潜在的应用价值,因此高选择性及亲和性的D3R配体的设计合成、结构优化及活性筛选成为研究热点。阿特维斯公司和匈牙利吉瑞大药厂开发的口服新药卡利拉嗪于2015年9月被FDA批准上市,作为一种对D3受体表现出更高亲和力的多巴胺D3/D2受体部分激动剂,用于治疗精神分裂症及双向躁郁症。介绍卡利拉嗪的研发背景、合成方法、临床药理学、临床评价、安全性和耐受性等研究概况。
[Key word]
[Abstract]
The dopamine D3 receptor (D3R) is a G protein-coupled receptor that belongs to the dopamine D2-like receptor family. It is preferentially expressed in limbic regions that are associated with cognitive and emotional functions. The D3R is an important therapeutic target of central disease, such as Parkinson's disease, schizophrenia, drug addiction, and so on. Now the design, synthesis, structural optimization, and pharmacological activity of high potency and selective D3R ligands attract more and more researchers' attention. Actavis Corp and Gedeon Richter Plc developed a new drug cariprazine as an orally active and potent dopamine D3-preferring D3/D2 receptor partial agonist, which was approved by FDA in September 2015 and could be used to treat idiopathic schizophrenia and bipolar disorder. This article introduces the overview of study on R&D background, synthetic method, clinical pharmacology, clinical evaluation, safety and tolerability, etc. of cariprazine.
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