2B确定:在药物发现中,色素受体2B的未来
Aaron M Bender1,2, Lauren C Parr1,2, William B Livingston3
1Warren Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, Tennessee 37232, United States.
Journal of medicinal chemistry
|August 16, 2023
概括
血清素5-HT2B受体激动剂引起心脏毒性,使其成为一个"抗目标". 然而,5-HT2B对抗剂在治疗肺动脉高血压和膜心脏病方面表现有前途.
科学领域:
- 药理学 药理学是指药理学的学科.
- 心血管医学 心血管医学
- 药物发现 药物发现 药物发现
背景情况:
- 血清素受体2B (5-HT2B) 与心脏毒性有关,范拉胺-胺 (-) 的使用就是一个例子.
- 这种心脏毒性将5-HT2B定位为一种
- 反目标反目标.
- 在药物发现中.
- 然而,5-HT2B对抗剂因其在心血管疾病中的治疗潜力而越来越受认可.
研究的目的:
- 审查芬的临床失败与5-HT2B研究之间的联系.
- 讨论选择性5-HT2B抗剂的发展.
- 检查5HT2B药物发现的当前景观,区分中枢神经系统和外围作用.
主要方法:
- 文献综述和对5HT2B受体药理学现有研究的综合.
- 分析与芬佛胺及其衍生物相关的临床数据.
- 对心血管疾病中的5-HT2B抗体进行临床前和临床研究的评估.
主要成果:
- 5-HT2B激动剂 (例如,诺芬拉胺) 的心脏毒性已得到充分证实.
- 5-HT2B对抗剂在肺动脉高血压 (PAH) 和膜心脏病 (VHD) 中显示出治疗潜力.
- 类似药物,选择性亚型5-HT2B抗剂的开发正在进行中.
结论:
- 尽管由于心脏毒性问题而导致历史上的挫折,5-HT2B对抗剂代表了对PAH和VHD的有前途的治疗类.
- 需要进一步的研究,以充分阐明5-HT2B对抗剂的治疗效用,特别是关于它们的中枢神经系统与外周作用.
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