Abstract
Since the discovery of the biological effects of adenosine, the development of potent and selective agonists and antagonists of adenosine receptors has been the subject of medicinal chemistry research for several decades, even if their clinical evaluation has been discontinued. Main problems include side effects due to the ubiquity of the receptors and the possibility of side effects, or to low brain penetration (in particular for the targeting of CNS diseases), short half-life of compounds, lack of effects. Furthermore, species differences in the affinity of ligands make difficult preclinical testing in animal models. Nevertheless, adenosine receptors continue to represent promising drug targets. A2A receptor has proved to be a promising pharmacological target for small synthetic ligands, and while A2A agonists are undergoing clinical trials for myocardial perfusion imaging and as anti-inflammatory agents, A2A antagonists represent an attractive field of research to discover new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease. Furthermore, the information coming from bioinformatics and molecular modeling studies for the A2A receptor has made easier the understanding of ligand-target interaction and the rational design of agonists and antagonists for this subtype. The aim of this review is to show an overview of the most significant steps and progresses in developing A2A adenosine receptor agonists and antagonists.
Keywords: Adenosine receptors, A2A adenosine receptor, A2A agonists and antagonists, nucleosides, xanthines, nitrogen heterocycles
Current Pharmaceutical Design
Title: A2A Adenosine Receptor and its Modulators: Overview on a Druggable GPCR and on Structure-Activity Relationship Analysis and Binding Requirements of Agonists and Antagonists
Volume: 14 Issue: 15
Author(s): G. Cristalli, C. Lambertucci, G. Marucci, R. Volpini and D. Dal Ben
Affiliation:
Keywords: Adenosine receptors, A2A adenosine receptor, A2A agonists and antagonists, nucleosides, xanthines, nitrogen heterocycles
Abstract: Since the discovery of the biological effects of adenosine, the development of potent and selective agonists and antagonists of adenosine receptors has been the subject of medicinal chemistry research for several decades, even if their clinical evaluation has been discontinued. Main problems include side effects due to the ubiquity of the receptors and the possibility of side effects, or to low brain penetration (in particular for the targeting of CNS diseases), short half-life of compounds, lack of effects. Furthermore, species differences in the affinity of ligands make difficult preclinical testing in animal models. Nevertheless, adenosine receptors continue to represent promising drug targets. A2A receptor has proved to be a promising pharmacological target for small synthetic ligands, and while A2A agonists are undergoing clinical trials for myocardial perfusion imaging and as anti-inflammatory agents, A2A antagonists represent an attractive field of research to discover new drugs for the treatment of neurodegenerative disorders, such as Parkinsons disease. Furthermore, the information coming from bioinformatics and molecular modeling studies for the A2A receptor has made easier the understanding of ligand-target interaction and the rational design of agonists and antagonists for this subtype. The aim of this review is to show an overview of the most significant steps and progresses in developing A2A adenosine receptor agonists and antagonists.
Export Options
About this article
Cite this article as:
Cristalli G., Lambertucci C., Marucci G., Volpini R. and Ben Dal D., A2A Adenosine Receptor and its Modulators: Overview on a Druggable GPCR and on Structure-Activity Relationship Analysis and Binding Requirements of Agonists and Antagonists, Current Pharmaceutical Design 2008; 14 (15) . https://dx.doi.org/10.2174/138161208784480081
DOI https://dx.doi.org/10.2174/138161208784480081 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Therapeutic Use of Δ9-THC and Cannabidiol: Evaluation of a New Extraction Procedure for the Preparation of Cannabis-based Olive Oil
Current Pharmaceutical Biotechnology Alzheimer’s Disease, Astrocytes and Kynurenines
Current Alzheimer Research CDK5 and MAPT Gene Expression in Alzheimer's Disease Brain Samples
Current Alzheimer Research Targeting Ras Activity Prevented Amyloid Beta-Induced Aberrant Neuronal Cell Cycle Re-Entry and Death
Current Alzheimer Research Podocyte Mitosis – A Catastrophe
Current Molecular Medicine Investigation of Isoprostanes as Potential Biomarkers for Alzheimer's Disease Using Chiral LC-MS/MS and SFC-MS/MS
Current Analytical Chemistry Tau, Amyloid Beta and Deep Brain Stimulation: Aiming to Restore Cognitive Deficit in Alzheimer's Disease
Current Alzheimer Research Clinical Trials for Neuroprotection in ALS
CNS & Neurological Disorders - Drug Targets Oxidative Stress in the Early Stage of Psychosis
Current Topics in Medicinal Chemistry Circulating Advanced Oxidation Protein Products as Oxidative Stress Biomarkers and Progression Mediators in Pathological Conditions Related to Inflammation and Immune Dysregulation
Current Medicinal Chemistry Induced Pluripotent Stem Cell-Based Studies of Parkinson's Disease: Challenges and Promises
CNS & Neurological Disorders - Drug Targets A Nanotechnological Approach to the Management of Alzheimer Disease and Type 2 Diabetes
CNS & Neurological Disorders - Drug Targets Fluoxetine Improves Behavioral Performance by Suppressing the Production of Soluble β-Amyloid in APP/PS1 Mice
Current Alzheimer Research Patent Selections
Recent Patents on Drug Delivery & Formulation Role of Fibroblast Growth Factor Receptors in Astrocytic Stem Cells
Current Signal Transduction Therapy Connection between JAK/STAT and PPARγ Signaling During the Progression of Multiple Sclerosis: Insights into the Modulation of T-Cells and Immune Responses in the Brain
Current Molecular Pharmacology A Review of Agents Patented for their Neuroprotective Properties
Recent Patents on CNS Drug Discovery (Discontinued) Neurobiology of Alzheimer’s Disease: Integrated Molecular, Physiological, Anatomical, Biomarker, and Cognitive Dimensions
Current Alzheimer Research The Molecular Pathology of Huntingtons Disease (HD)
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents Ketamine: New Indications for an Old Drug
Current Drug Targets