Abstract
Mineralocorticoid receptor (MR) antagonism has proven to effectively attenuate the pathophysiological effects of aldosterone in clinical and experimental settings of hypertension and heart failure. MR activates transcription of target genes upon aldosterone binding, and eplerenone selectively binds to MR and blocks aldosterone- mediated activation. In this review, we summarize the preclinical and clinical evidence supporting the beneficial effects of eplerenone (INSPRATM), a selective aldosterone blocker, in the treatment of hypertension and heart failure. We also review the current status in understanding the molecular mechanisms of action of the MR and its ligand. In addition, we compare the effects of eplerenone and spironolactone, a nonselective aldosterone blocker, on the transcriptional activity of MR and provide a molecular explanation for the improved side-effect profile of eplerenone compared with spironolactone.
Keywords: hypertension, reninangiotensin-aldosterone system, angiotensin-converting enzyme, aldosterone antagonist., antihypertensive, histone acetyltransferase, cortical collecting tubule
Mini-Reviews in Medicinal Chemistry
Title: Molecular Mechanisms of Mineralocorticoid Receptor Antagonism by Eplerenone
Volume: 5 Issue: 8
Author(s): Xiao Hu, Suzhen Li, Ellen G. McMahon, Deepak S. Lala and Amy E. Rudolph
Affiliation:
Keywords: hypertension, reninangiotensin-aldosterone system, angiotensin-converting enzyme, aldosterone antagonist., antihypertensive, histone acetyltransferase, cortical collecting tubule
Abstract: Mineralocorticoid receptor (MR) antagonism has proven to effectively attenuate the pathophysiological effects of aldosterone in clinical and experimental settings of hypertension and heart failure. MR activates transcription of target genes upon aldosterone binding, and eplerenone selectively binds to MR and blocks aldosterone- mediated activation. In this review, we summarize the preclinical and clinical evidence supporting the beneficial effects of eplerenone (INSPRATM), a selective aldosterone blocker, in the treatment of hypertension and heart failure. We also review the current status in understanding the molecular mechanisms of action of the MR and its ligand. In addition, we compare the effects of eplerenone and spironolactone, a nonselective aldosterone blocker, on the transcriptional activity of MR and provide a molecular explanation for the improved side-effect profile of eplerenone compared with spironolactone.
Export Options
About this article
Cite this article as:
Hu Xiao, Li Suzhen, McMahon G. Ellen, Lala S. Deepak and Rudolph E. Amy, Molecular Mechanisms of Mineralocorticoid Receptor Antagonism by Eplerenone, Mini-Reviews in Medicinal Chemistry 2005; 5 (8) . https://dx.doi.org/10.2174/1389557054553811
DOI https://dx.doi.org/10.2174/1389557054553811 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Mitochondria as a Therapeutic Target in Metabolic Disorders
Mitochondria are the primary site of adenosine triphosphate (ATP) production in mammalian cells. Moreover, these organelles are an important source of reactive oxygen and nitrogen species in virtually any nucleated cell type. The modulation of a myriad of cellular signaling pathways depends on the mitochondrial physiology. Mitochondrial dysfunction is observed ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Redox State, Oxidative Stress, and Molecular Mechanisms of Protective and Toxic Effects of Bilirubin on Cells
Current Pharmaceutical Design Metformin in the Treatment of Polycystic Ovary Syndrome
Current Pharmaceutical Design The Cytoprotective and Anti-cancer Potential of Bisbenzylisoquinoline Alkaloids from <I>Nelumbo nucifera</I>
Current Topics in Medicinal Chemistry Treatment of the Cheyne-Stokes Breathing Pattern in Patients with Congestive Heart Failure: State of the Art
Current Respiratory Medicine Reviews Vagal Stimulation Facilitates Improving Effects of Ranolazine on Cardiac Function in Rats with Chronic Ischemic Heart Failure
Current Molecular Medicine High-Density Lipoprotein at the Interface of Type 2 Diabetes Mellitus And Cardiovascular Disorders
Current Pharmaceutical Design Atherosclerotic and Non-Atherosclerotic Coronary Heart Disease in Women
Current Medicinal Chemistry PDE-5 Inhibitors for BPH-Associated LUTS
Current Drug Targets Notch Signaling: A Potential Therapeutic Target in Prostate Cancer
Current Cancer Drug Targets The Roles of Cytochrome P450 in Ischemic Heart Disease
Current Drug Metabolism Glucagon-like Peptide-1 Receptor Agonists Cardio-protective Effects: An Umbrella Review
Current Diabetes Reviews Matrix Metallopropteinases in Heart Failure
Current Topics in Medicinal Chemistry Dronedarone – A New Alternative for Management of Atrial Fibrillation
Recent Patents on Cardiovascular Drug Discovery Cranberry as Promising Natural Source of Potential Anticancer Agents: Current Evidence and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Regulation of Angiogenesis by Macrophages, Dendritic Cells, and Circulating Myelomonocytic Cells
Current Pharmaceutical Design Anti-Inflammatory Agents in Ageing and Age-Associated Diseases
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry PPAR-γ: Therapeutic Prospects in Parkinson's Disease
Current Drug Targets Trends in Mitochondrial Therapeutics for Neurological Disease
Current Medicinal Chemistry Isothiocyanates as Cancer Chemopreventive Agents: Their Biological Activities and Metabolism in Rodents and Humans
Current Drug Metabolism Pharmacokinetic-Pharmacodynamic Modeling of Antihypertensive Drugs: From Basic Research to Clinical Practice
Current Hypertension Reviews