多巴胺D3受體(D3R)是一種G蛋白偶聯(lián)的D2樣受體,多表達(dá)于與認(rèn)知、情緒等腦機(jī)能密切相關(guān)的邊緣區(qū)域。以D3R為靶標(biāo)治療帕金森病、精神分裂癥及藥物成癮等中樞神經(jīng)系統(tǒng)疾病具有潛在的應(yīng)用價(jià)值,因此高選擇性及親和性的D3R配體的設(shè)計(jì)合成、結(jié)構(gòu)優(yōu)化及活性篩選成為研究熱點(diǎn)。阿特維斯公司和匈牙利吉瑞大藥廠開(kāi)發(fā)的口服新藥卡利拉嗪于2015年9月被FDA批準(zhǔn)上市,作為一種對(duì)D3受體表現(xiàn)出更高親和力的多巴胺D3/D2受體部分激動(dòng)劑,用于治療精神分裂癥及雙向躁郁癥。介紹卡利拉嗪的研發(fā)背景、合成方法、臨床藥理學(xué)、臨床評(píng)價(jià)、安全性和耐受性等研究概況。

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.