Abstract
Adenosines diverse physiological functions are mediated by four subtypes of receptors (A1, A2A, A2B and A3). The A1 adenosine receptor pharmacology and therapeutic application of ligands for this receptor are the subjects of this review. A1 receptors are present on the surface of cells in organs throughout the body. Actions mediated by A1 receptors include slowing of heart rate and AV nodal conduction, reduction of atrial contractility, attenuation of the stimulatory actions of catecholamines on beta-adrenergic receptors, reduction of lipolysis in adipose tissue, reduction of urine formation, and inhibition of neuronal activity. Although adenosine analogs with high efficacy, affinity, and selectivity for the A1 receptor are available, the ubiquitous distribution and wide range of physiological actions mediated by A1 receptors are obstacles to development of therapeutic agents that activate these receptors. However, it may be possible to exploit the high A1 “receptor reserve” for some actions of adenosine by use of weak (partial) agonists to target these actions while avoiding others for which receptor reserve is low. The presence of high receptor reserves for the anti-arrhythmic and anti-lipolytic actions of adenosine suggests that partial A1 agonists could be used as anti-arrhythmic and anti-lipolytic agents. In addition, allosteric enhancers of the binding of adenosine to A1 receptors could be used therapeutically to potentiate desirable effects of endogenous adenosine. Antagonists of the A1 receptor can increase urine formation, and because they do not decrease renal blood flow, are particularly useful to maintain glomerular filtration in patients having edema secondary to reduced cardiac function.
Keywords: adenosine, a1 receptor, anti-arrhythmic, anti-lipolytic, g protein-coupled receptor (gpcr)
Current Topics in Medicinal Chemistry
Title: Pharmacology and Therapeutic Applications of A1 Adenosine Receptor Ligands
Volume: 3 Issue: 4
Author(s): Arvinder K. Dhalla, John C. Shryock, Revati Shreeniwas and Luiz Belardinelli
Affiliation:
Keywords: adenosine, a1 receptor, anti-arrhythmic, anti-lipolytic, g protein-coupled receptor (gpcr)
Abstract: Adenosines diverse physiological functions are mediated by four subtypes of receptors (A1, A2A, A2B and A3). The A1 adenosine receptor pharmacology and therapeutic application of ligands for this receptor are the subjects of this review. A1 receptors are present on the surface of cells in organs throughout the body. Actions mediated by A1 receptors include slowing of heart rate and AV nodal conduction, reduction of atrial contractility, attenuation of the stimulatory actions of catecholamines on beta-adrenergic receptors, reduction of lipolysis in adipose tissue, reduction of urine formation, and inhibition of neuronal activity. Although adenosine analogs with high efficacy, affinity, and selectivity for the A1 receptor are available, the ubiquitous distribution and wide range of physiological actions mediated by A1 receptors are obstacles to development of therapeutic agents that activate these receptors. However, it may be possible to exploit the high A1 “receptor reserve” for some actions of adenosine by use of weak (partial) agonists to target these actions while avoiding others for which receptor reserve is low. The presence of high receptor reserves for the anti-arrhythmic and anti-lipolytic actions of adenosine suggests that partial A1 agonists could be used as anti-arrhythmic and anti-lipolytic agents. In addition, allosteric enhancers of the binding of adenosine to A1 receptors could be used therapeutically to potentiate desirable effects of endogenous adenosine. Antagonists of the A1 receptor can increase urine formation, and because they do not decrease renal blood flow, are particularly useful to maintain glomerular filtration in patients having edema secondary to reduced cardiac function.
Export Options
About this article
Cite this article as:
Dhalla K. Arvinder, Shryock C. John, Shreeniwas Revati and Belardinelli Luiz, Pharmacology and Therapeutic Applications of A1 Adenosine Receptor Ligands, Current Topics in Medicinal Chemistry 2003; 3 (4) . https://dx.doi.org/10.2174/1568026033392246
DOI https://dx.doi.org/10.2174/1568026033392246 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...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
- Announcements
Related Articles
-
Lipid Lowering Agents, Inflammation and Atherosclerosis
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Statins: Are They All the Same?
Current Drug Therapy Research and Development of Nuclear Molecular Imaging in Taiwan
Current Medical Imaging Regression of Oxidative Stress by Targeting eNOS and Nrf2/ARE Signaling: A Guided Drug Target for Cardiovascular Diseases
Current Topics in Medicinal Chemistry Computational Approaches for the Prediction of Protein-Protein Interactions: A Survey
Current Bioinformatics Heart Failure in Diabetes Mellitus: An Updated Review
Current Pharmaceutical Design Thyroid Hormone-Induced Angiogenesis
Current Cardiology Reviews Management of Blood Pressure and Heart Rate in Acute Decompensated Heart Failure with Volume Overload
Current Pharmaceutical Design Old Tyrosine Kinase Inhibitors and Newcomers in Gastrointestinal Cancer Treatment
Current Cancer Drug Targets The Role of Dronedarone in the Treatment of Atrial Fibrillation/Flutter in the Aftermath of PALLAS
Current Cardiology Reviews Homocysteine, Intracellular Signaling and Thrombotic Disorders
Current Medicinal Chemistry Sundowning Syndrome: A Possible Marker of Frailty in Alzheimer’s Disease?
CNS & Neurological Disorders - Drug Targets Beyond the Cardiac Myofilament: Hypertrophic Cardiomyopathy- Associated Mutations in Genes that Encode Calcium-Handling Proteins
Current Molecular Medicine Different Types of Cell Death in Organismal Aging and Longevity: State of the Art and Possible Systems Biology Approach
Current Pharmaceutical Design Functional Relevance of Biased Signaling at the Angiotensin II Type 1 Receptor
Endocrine, Metabolic & Immune Disorders - Drug Targets Altered Hyaluronan Biosynthesis and Cancer Progression: an Immunological Perspective
Mini-Reviews in Medicinal Chemistry Histone Deacetylase Inhibitors: An Attractive Strategy for Cancer Therapy
Current Medicinal Chemistry A Decade of Targets and Patented Drugs for Chemotherapy of Chagas Disease
Recent Patents on Anti-Infective Drug Discovery Metabolomics Analysis for Biomarker Discovery: Advances and Challenges
Current Medicinal Chemistry Real-Time Location, Position and Motion Data for Healthcare Information Systems – A Patent Review
Recent Advances in Communications and Networking Technology (Discontinued)