Abstract
The current pharmacological therapies for the treatment of Parkinson’s disease are mostly inadequate and recent, improved therapeutic agents are required. Two important molecular targets for the design of anti-parkinsonian therapeutic compounds are the adenosine A2A receptor and the enzyme, monoamine oxidase (MAO) B. Adenosine A2A receptor antagonists are a relatively new class of anti-parkinsonian agents, which act by potentiating dopamine-mediated neurotransmission via dopamine D2 receptors. MAO-B inhibitors are established therapy of Parkinson’s disease and inhibit the MAO-B-catalysed metabolism of dopamine in the brain. This conserves reduced dopamine stores and extends the action of dopamine. A2A antagonism and MAO-B inhibition have also been associated with neuroprotective effects, further establishing roles for these classes of compounds in Parkinson’s disease. Interestingly, caffeine, a known adenosine receptor antagonist, has been recently considered as a lead compound for the design and discovery of A2A antagonists and MAO-B inhibitors. This review summarizes the recent efforts to discover caffeinederived MAO-B inhibitors. The design of caffeine-derived A2A antagonists has been extensively reviewed previously. The prospect of discovering dual-target-directed compounds that act at both targets is also evaluated. Compounds that block the activation and function of both A2A receptors and MAO-B may have a synergistic effect in the treatment of patients with Parkinson’s disease.
Keywords: Adenosine A2A receptor, caffeine, drug design, dual-target-directed, inhibition, monoamine oxidase, Parkinson’s disease.
Current Medicinal Chemistry
Title:Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease
Volume: 22 Issue: 8
Author(s): Jacobus P. Petzer and Anel Petzer
Affiliation:
Keywords: Adenosine A2A receptor, caffeine, drug design, dual-target-directed, inhibition, monoamine oxidase, Parkinson’s disease.
Abstract: The current pharmacological therapies for the treatment of Parkinson’s disease are mostly inadequate and recent, improved therapeutic agents are required. Two important molecular targets for the design of anti-parkinsonian therapeutic compounds are the adenosine A2A receptor and the enzyme, monoamine oxidase (MAO) B. Adenosine A2A receptor antagonists are a relatively new class of anti-parkinsonian agents, which act by potentiating dopamine-mediated neurotransmission via dopamine D2 receptors. MAO-B inhibitors are established therapy of Parkinson’s disease and inhibit the MAO-B-catalysed metabolism of dopamine in the brain. This conserves reduced dopamine stores and extends the action of dopamine. A2A antagonism and MAO-B inhibition have also been associated with neuroprotective effects, further establishing roles for these classes of compounds in Parkinson’s disease. Interestingly, caffeine, a known adenosine receptor antagonist, has been recently considered as a lead compound for the design and discovery of A2A antagonists and MAO-B inhibitors. This review summarizes the recent efforts to discover caffeinederived MAO-B inhibitors. The design of caffeine-derived A2A antagonists has been extensively reviewed previously. The prospect of discovering dual-target-directed compounds that act at both targets is also evaluated. Compounds that block the activation and function of both A2A receptors and MAO-B may have a synergistic effect in the treatment of patients with Parkinson’s disease.
Export Options
About this article
Cite this article as:
Petzer P. Jacobus and Petzer Anel, Caffeine as a Lead Compound for the Design of Therapeutic Agents for the Treatment of Parkinson’s Disease, Current Medicinal Chemistry 2015; 22 (8) . https://dx.doi.org/10.2174/0929867322666141215160015
DOI https://dx.doi.org/10.2174/0929867322666141215160015 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
-
Side Effects of Atypical Antipsychotic Drugs
Current Pharmaceutical Design Computational Studies of Molecular Targets Regarding the Adverse Effects of Isoniazid Drug for Tuberculosis
Current Pharmacogenomics and Personalized Medicine Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate
Current Drug Discovery Technologies New Adamantane Derivatives with Sigma Affinity and Antiproliferative Activity
Medicinal Chemistry GABA Receptors: Pharmacological Potential and Pitfalls
Current Pharmaceutical Design Characterisation of a Neural Teratogenicity Assay Based on Human ESCs Differentiation Following Exposure to Valproic Acid
Current Medicinal Chemistry Voltage-Gated Calcium Channels as Targets for the Treatment of Chronic Pain
Current Drug Targets - CNS & Neurological Disorders Patient’s Perceptions of the Cannabis-psychosis Link - A Systematic Review
Current Pharmaceutical Design Single Channel EEG Signal for Automatic Detection of Absence Seizure Using Convolutional Neural Network
Recent Advances in Computer Science and Communications Cooling the Injured Brain: How Does Moderate Hypothermia Influence the Pathophysiology of Traumatic Brain Injury
Current Pharmaceutical Design Evaluation of the Influence of the Conjugation Site of the Chelator Agent HYNIC to GLP1 Antagonist Radiotracer for Insulinoma Diagnosis
Current Radiopharmaceuticals Pathophysiological Role of Mitochondrial Potassium Channels and their Modulation by Drugs
Current Medicinal Chemistry Adenosine and ATP Receptors in the Brain
Current Topics in Medicinal Chemistry Lack of Data on Depression-like States and Antidepressant Pharmacotherapy in Patients with Epilepsy: Randomised Controlled Trials are Badly Needed
Current Pharmaceutical Design HtrA Serine Proteases as Potential Therapeutic Targets in Cancer
Current Cancer Drug Targets Histone Acetylation in Neurodevelopment
Current Pharmaceutical Design Drug Transport Across the Blood-Brain Barrier and the Impact of Breast Cancer Resistance Protein (ABCG2)
Current Topics in Medicinal Chemistry Extracts of Bacopa monnieri (L) Pennell Down-Regulate the Expression of Leukotriene C<sub>4</sub> Synthase mRNA in HL-60 Cells and Suppress OVAInduced Inflammation in BALB/c Mice
Current Bioactive Compounds A Systematic Review of Plant-Derived Natural Compounds for Anxiety Disorders
Current Topics in Medicinal Chemistry Editorial (Thematic Issue: In vivo MRS: Techniques and Applications)
Current Molecular Imaging (Discontinued)