Samidurai Arun, Xi Lei, Das Anindita, Kukreja Rakesh C
Division of Cardiology, Pauley Heart Center, Virginia Commonwealth University, Richmond, Virginia, USA; email:
Annu Rev Pharmacol Toxicol. 2023 Jan 20;63:585-615. doi: 10.1146/annurev-pharmtox-040122-034745. Epub 2022 Oct 7.
Cyclic guanosine monophosphate (cGMP), an important intracellular second messenger, mediates cellular functional responses in all vital organs. Phosphodiesterase 5 (PDE5) is one of the 11 members of the cyclic nucleotide phosphodiesterase (PDE) family that specifically targets cGMP generated by nitric oxide-driven activation of the soluble guanylyl cyclase. PDE5 inhibitors, including sildenafil and tadalafil, are widely used for the treatment of erectile dysfunction, pulmonary arterial hypertension, and certain urological disorders. Preclinical studies have shown promising effects of PDE5 inhibitors in the treatment of myocardial infarction, cardiac hypertrophy, heart failure, cancer and anticancer-drug-associated cardiotoxicity, diabetes, Duchenne muscular dystrophy, Alzheimer's disease, and other aging-related conditions. Many clinical trials with PDE5 inhibitors have focused on the potential cardiovascular, anticancer, and neurological benefits. In this review, we provide an overview of the current state of knowledge on PDE5 inhibitors and their potential therapeutic indications for various clinical disorders beyond erectile dysfunction.
环磷酸鸟苷（cGMP）是一种重要的细胞内第二信使，介导所有重要器官的细胞功能反应。磷酸二酯酶5（PDE5）是环核苷酸磷酸二酯酶（PDE）家族11个成员之一，它特异性作用于一氧化氮驱动可溶性鸟苷酸环化酶激活所产生的cGMP。包括西地那非和他达拉非在内的PDE5抑制剂被广泛用于治疗勃起功能障碍、肺动脉高压和某些泌尿系统疾病。临床前研究表明，PDE5抑制剂在治疗心肌梗死、心脏肥大、心力衰竭、癌症及抗癌药物相关心脏毒性、糖尿病、杜氏肌营养不良症、阿尔茨海默病和其他与衰老相关的病症方面具有良好效果。许多使用PDE5抑制剂的临床试验都聚焦于其潜在的心血管、抗癌和神经方面的益处。在本综述中，我们概述了关于PDE5抑制剂的当前知识状态及其在勃起功能障碍以外的各种临床疾病中的潜在治疗适应证。
