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.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1146/annurev-pharmtox-040122-034745 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Defining proteoform-specific interactions for drug targeting in a native cell signalling environment.
Nat Chem
January 2025
Physical and Theoretical Chemistry Laboratory, Department of Chemistry, University of Oxford, Oxford, UK.
Understanding the dynamics of membrane protein-ligand interactions within a native lipid bilayer is a major goal for drug discovery. Typically, cell-based assays are used, however, they are often blind to the effects of protein modifications. In this study, using the archetypal G protein-coupled receptor rhodopsin, we found that the receptor and its effectors can be released directly from retina rod disc membranes using infrared irradiation in a mass spectrometer.
View Article and Find Full Text PDFIsolation and identification of two novel PDE-5 inhibitors illegally added to pressed candies.
Food Addit Contam Part A Chem Anal Control Expo Risk Assess
January 2025
Shanxi Key Laboratory of Food and Drug Safety Prevention and Control, Inspection and Testing Center of Shanxi Province, Taiyuan, Shanxi, China.
Two novel phosphodiesterase 5 (PDE-5) inhibitors were detected in pressed candy using high-performance liquid chromatography (HPLC)-diode array detection. Following extraction with acetonitrile and sonication, the compounds were isolated and purified semi-preparative liquid chromatography. Structural characterisation was achieved through high-resolution mass spectrometry (HRMS) and nuclear magnetic resonance (NMR) spectroscopy.
View Article and Find Full Text PDFFrom Antipsychotic to Neuroprotective: Computational Repurposing of Fluspirilene as a Potential PDE5 Inhibitor for Alzheimer's Disease.
J Comput Chem
January 2025
Centre for Inflammation, Centenary Institute and University of Technology Sydney, Faculty of Science, School of Life Sciences, Sydney, New South Wales, Australia.
Phosphodiesterase 5 (PDE5) inhibitors have shown great potential in treating Alzheimer's disease by improving memory and cognitive function. In this study, we evaluated fluspirilene, a drug commonly used to treat schizophrenia, as a potential PDE5 inhibitor using computational methods. Molecular docking revealed that fluspirilene binds strongly to PDE5, supported by hydrophobic and aromatic interactions.
View Article and Find Full Text PDFPhosphodiesterase-5 Inhibitors Show Promise in Improving Survival for Patients With COPD Pulmonary Hypertension: One Step Further But There Is Still a Long Way to Go.
Chest
January 2025
Pulmonary Division, Lady Davis Carmel Medical Center, Faculty of Medicine Technion Institute of Technology, Haifa, Israel.
Vitamin D as an add-on therapy to phosphodiesterase-5 inhibitor in experimental pulmonary arterial hypertension.
Am J Physiol Lung Cell Mol Physiol
January 2025
Department of Pharmacology and Toxicology. School of Medicine, Universidad Complutense de Madrid, Madrid, Spain.
Severe vitamin D (vitD) deficiency is a very common condition in patients with pulmonary arterial hypertension (PAH) and it is predictor of poor prognosis. There is emerging evidence suggesting a connection between the insufficient response to phosphodiesterase-5 inhibitors (PDE5i) and vitD deficiency in patients with PAH. In the present translational study, vitD deficiency was induced in Wistar rats by exposure to vitD free diet for 5 weeks and followed by Su5416 administration and hypoxia (10%) for 3 weeks, a standard experimental model of PAH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!