Beyond Erectile Dysfunction: cGMP-Specific Phosphodiesterase 5 Inhibitors for Other Clinical Disorders.

IF 11.2 1区医学 Q1 PHARMACOLOGY & PHARMACY

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI:10.1146/annurev-pharmtox-040122-034745

Arun Samidurai, Lei Xi, Anindita Das, Rakesh C Kukreja

{"title":"Beyond Erectile Dysfunction: cGMP-Specific Phosphodiesterase 5 Inhibitors for Other Clinical Disorders.","authors":"Arun Samidurai, Lei Xi, Anindita Das, Rakesh C Kukreja","doi":"10.1146/annurev-pharmtox-040122-034745","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":null,"pages":null},"PeriodicalIF":11.2000,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"6","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual review of pharmacology and toxicology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-pharmtox-040122-034745","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}

引用次数: 6

Abstract

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.

查看原文本刊更多论文

超越勃起功能障碍:cgmp特异性磷酸二酯酶5抑制剂治疗其他临床疾病。

环鸟苷单磷酸(cGMP)是一种重要的细胞内第二信使，介导了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)家族的11个成员之一，专门针对由一氧化氮驱动的可溶性鸟酰环化酶激活产生的cGMP。PDE5抑制剂，包括西地那非和他达拉非，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、心肌肥厚、心力衰竭、癌症和抗癌药物相关的心脏毒性、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疾病方面具有良好的效果。许多PDE5抑制剂的临床试验都集中在潜在的心血管、抗癌和神经系统益处上。在这篇综述中，我们概述了PDE5抑制剂的现状及其对勃起功能障碍以外的各种临床疾病的潜在治疗适应症。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Annual review of pharmacology and toxicology 医学-毒理学

CiteScore

27.80

自引率

0.00%

发文量

期刊介绍： Since 1961, the Annual Review of Pharmacology and Toxicology has been a comprehensive resource covering significant developments in pharmacology and toxicology. The journal encompasses various aspects, including receptors, transporters, enzymes, chemical agents, drug development science, and systems like the immune, nervous, gastrointestinal, cardiovascular, endocrine, and pulmonary systems. Special topics are also featured in this annual review.