首页 / 院系成果 / 成果详情页

Compound 38, a novel potent and selective antagonist of adenosine A_2A receptor, enhances arousal in mice 期刊论文

编号：

1A40123E7F6FFF133B5D07CC36C14B27
作者：

Zhang, Hui#^[1,2,3]Ma, Weixiang#^[2,3]Xie, Qiong#^[4]Bu, Lifang^[2];Kong, Lingxi^[2];Yuan, Pingchuan^[1,2];Zhou, Ronghui^[4];Wang, Yonghui^[4];Wu, Lei^[4];Zhu, Chenyu^[4];Wang, Zhilin^[2];Han, Jun(韩军)*^[1,5]Huang, Zhili*^[2,6]Wang, Yiqun*^[2]
语种：

英文
期刊：

ACTA PHARMACOLOGICA SINICA ISSN：1671-4083 2025 年 46 卷 5 期 (1177 - 1189) ; MAY
收录：
关键词：

Compound <bold>38</bold> A(2A)R antagonist arousal-promoting effect sleep-wake states sleep deprivation A(2A)R KO mice
摘要：

Adenosine A(2A) receptor (A(2A)R) plays a pivotal role in the regulation of sleep-wake behaviors. We previously reported an A(2A)R selective antagonist compound 38 with an IC50 value of 29.0 nM. In this study, we investigated its effect on sleep-wake regulation in mice. Wild-type (WT) mice were administered compound 38 (3.3, 5.0, 7.5, 15, 30 mg/kg, i.p.) at 9:00, and electroencephalography and electromyography were simultaneously recorded. We showed that administration of compound 38 exhibited a dose-dependent effect on wakefulness promotion. To investigate the impact of compound 38 on sleep rebound, we conducted a 6 h (13:00-19:00) sleep deprivation experiment. We found that administration of compound 38 (30 mg/kg) produced a wakefulness-promoting effect lasting for 1 h. Subsequently, we explored the critical role of A(2A)R in the wakefulness-promoting effect of compound 38 using A(2A)R knockout (KO) mice and their WT littermates. We found that compound 38 enhanced wakefulness in WT mice, but did not have an arousal-promoting effect in A(2A)R KO mice, suggesting that the arousal-promoting effect of compound 38 was mediated by A(2A)R. We conducted immunohistochemistry and selectively ablated A(2A)R-positive neurons using cell type-specific caspase-3 expression, which revealed an essential role of A(2A)R-positive neurons in the nucleus accumbens shell for the arousal-promoting effect of compound 38. In conclusion, as a novel A(2A)R antagonist, compound 38 promotes wakefulness in mice via the A(2A)R and exhibits promising applications for further advancements in the field of sleep-wake disorders.
推荐引用方式
GB/T 7714：

Zhang Hui,Ma Wei-xiang,Xie Qiong, et al. Compound 38, a novel potent and selective antagonist of adenosine A_2A receptor, enhances arousal in mice [J].ACTA PHARMACOLOGICA SINICA,2025,46(5):1177-1189.
APA：

Zhang Hui,Ma Wei-xiang,Xie Qiong,Bu Li-fang,&Wang Yi-qun.(2025).Compound 38, a novel potent and selective antagonist of adenosine A_2A receptor, enhances arousal in mice .ACTA PHARMACOLOGICA SINICA,46(5):1177-1189.
MLA：

Zhang Hui, et al. "Compound 38, a novel potent and selective antagonist of adenosine A_2A receptor, enhances arousal in mice" .ACTA PHARMACOLOGICA SINICA 46,5(2025):1177-1189.
入库时间：

1/20/2025 9:17:24 PM
更新时间：

2/10/2025 9:45:53 PM
条目包含文件：

文件类型： , 文件大小：

正在加载全文

未找到全文

浏览次数：219  下载次数：0

分享到：

浏览次数：219

下载次数：0

打印次数：0

Compound 38, a novel potent and selective antagonist of adenosine A2A receptor, enhances arousal in mice 期刊论文

Compound 38, a novel potent and selective antagonist of adenosine A_2A receptor, enhances arousal in mice 期刊论文