环磷鸟苷酸（cGMP）是一种重要的细胞内次信使，在所有重要器官中介导细胞功能反应。磷酸二酯酶5（PDE5）是环核苷酸磷酸二酯酶（PDE）家族中的11个成员之一，专门针对由一氧化氮驱动的可溶性鸟苷酸环化酶产生的cGMP。包括西地那非和他达拉非在内的PDE5抑制剂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。动物实验研究显示PDE5抑制剂在心肌梗死、心脏肥大、心衰、癌症及抗癌药物相关心脏毒性、糖尿病、杜氏肌萎缩症、阿尔茨海默病和其他与衰老相关疾病的治疗方面有着有希望的效果。许多临床试验关注PDE5抑制剂的潜在心血管、抗癌和神经学益处。在本综述中，我们提供有关PDE5抑制剂及其治疗超越勃起功能障碍的各种临床疾病的潜在适应症的知识概述。

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.