Repurposing of the PDE5 Inhibitor Sildenafil for the Treatment of Persistent Pulmonary Hypertension in Neonates

doi:10.2174/0929867327666200923151924
摘要

一氧化氮(NO)是血管内皮细胞和神经释放的重要内源性信号分子，它激活酶可溶性鸟苷酸环化酶，催化三磷酸鸟苷合成环状单磷酸鸟苷(cGMP)。反过来，cGMP激活蛋白激酶G磷酸化平滑肌细胞中的一系列效应蛋白，从而降低细胞内Ca2+水平以抑制收缩和增殖。磷酸二酯酶5型(PDE5)通过将cGMP水解成不活跃的5 '' -GMP，从而抑制其作用。小分子PDE5抑制剂(PDE5is)，如西地那非，可以延长cGMP的可用性，从而增强no介导的信号转导。pde5是治疗勃起功能障碍的一线药物，但现在也被批准用于成人肺动脉高压(PAH)的治疗。新生儿持续性肺动脉高压(PPHN)目前使用吸入NO治疗，但这是一种昂贵的选择，约1/3的新生儿无反应，导致需要其他方法。本文综述了PDE5的发展、化学和药理学，以及西地那非用于勃起功能障碍和PAH的应用，并对西地那非作为PPHN治疗的进一步再利用的当前证据进行了严格的回顾。
关键词: 西地那非，一氧化氮，肺动脉高压，磷酸二酯酶抑制剂，环GMP，新生儿
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DOI https://dx.doi.org/10.2174/0929867327666200923151924	Print ISSN 0929-8673
Publisher Name Bentham Science Publisher	Online ISSN 1875-533X
当代药物化学

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当代药物化学

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