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Review Article

针对嘌呤能P2X7受体的抗抑郁药的最新进展

卷 30, 期 2, 2023

发表于: 29 August, 2022

页: [164 - 177] 页: 14

弟呕挨: 10.2174/0929867329666220629141418

价格: $65

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摘要

嘌呤能P2X7受体(P2X7R)是一种三磷酸腺苷(ATP)门控阳离子通道蛋白。尽管在正常情况下，细胞外ATP (eATP)保持在纳摩尔浓度范围内，但在细胞应激或损伤时，它会升高到微摩尔水平，导致大脑中P2X7R的激活。eATP与大脑胶质细胞P2X7R的结合激活NLRP3炎性小体，并释放促炎细胞因子，如IL-1β， IL-6, IL-18和TNFα。抑郁症已被证明与P2X7R激活的神经炎症密切相关。因此，P2X7R是一个有吸引力的治疗抑郁症的靶点。包括阿斯利康(AstraZeneca)、葛兰素史克(GlaxoSmithKline)、杨森(Janssen)、灵贝克(Lundbeck)和辉瑞(Pfizer)在内的跨国制药公司已经开发了可穿透CNS的P2RX7拮抗剂。其中一些已经在临床试验中进行了评估。本文综述了近年来P2X7R拮抗剂作为新型抗抑郁药物的结构优化、代表性化合物的体内外评价和理化性质等方面的研究进展。

关键词: 嘌呤能P2X7受体，抑郁，神经炎症，ATP，构效关系，血脑屏障渗透。

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