Abstract
Parkinsons disease (PD) is a progressive neurodegenerative disorder that results in major motor disturbances due primarily to loss of midbrain dopamine neurons. The mainstream treatment has been dopaminergic replacement therapy aimed at symptomatic relief, with the gold standard drug being the dopamine precursor levodopa. The general dogma has been that levodopa works primarily by indirectly activating the D2 family of dopamine receptors. Recently, a number of direct dopamine agonists that target the D2 and D3 dopamine receptors have been used as dopaminergic replacement strategies. Although these direct D2 and D3 drugs cause only modest improvement in motor function compared to levodopa, they can delay the initiation of levodopa and can act synergistically with levodopa. In addition, they can delay the onset of levodopa-related motor complications. Recent imaging data also suggest that they may have neuroprotective effects. Whereas D2/D3 agonists have received much attention as several drugs are available for clinical trials and usage, there has been a large body of data showing that the D1 receptor actually may play a larger role in restoration of normal motor function. This review examines the current use of dopamine D2/D3 agonists in treatment of PD and their potential for providing neuroprotection. Furthermore, we also examine the potential that D1 agonists might have in neuroprotective actions in the disease progression.
Keywords: Dopamine, D1, agonist, neuroprotection, Parkinson's disease
CNS & Neurological Disorders - Drug Targets
Title: D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinsons Disease
Volume: 5 Issue: 3
Author(s): M. M. Lewis, X. Huang, D. E. Nichols and R. B. Mailman
Affiliation:
Keywords: Dopamine, D1, agonist, neuroprotection, Parkinson's disease
Abstract: Parkinsons disease (PD) is a progressive neurodegenerative disorder that results in major motor disturbances due primarily to loss of midbrain dopamine neurons. The mainstream treatment has been dopaminergic replacement therapy aimed at symptomatic relief, with the gold standard drug being the dopamine precursor levodopa. The general dogma has been that levodopa works primarily by indirectly activating the D2 family of dopamine receptors. Recently, a number of direct dopamine agonists that target the D2 and D3 dopamine receptors have been used as dopaminergic replacement strategies. Although these direct D2 and D3 drugs cause only modest improvement in motor function compared to levodopa, they can delay the initiation of levodopa and can act synergistically with levodopa. In addition, they can delay the onset of levodopa-related motor complications. Recent imaging data also suggest that they may have neuroprotective effects. Whereas D2/D3 agonists have received much attention as several drugs are available for clinical trials and usage, there has been a large body of data showing that the D1 receptor actually may play a larger role in restoration of normal motor function. This review examines the current use of dopamine D2/D3 agonists in treatment of PD and their potential for providing neuroprotection. Furthermore, we also examine the potential that D1 agonists might have in neuroprotective actions in the disease progression.
Export Options
About this article
Cite this article as:
Lewis M. M., Huang X., Nichols E. D. and Mailman B. R., D1 and Functionally Selective Dopamine Agonists as Neuroprotective Agents in Parkinsons Disease, CNS & Neurological Disorders - Drug Targets 2006; 5 (3) . https://dx.doi.org/10.2174/187152706777452245
DOI https://dx.doi.org/10.2174/187152706777452245 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...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
-
The Emerging Role of MicroRNA in Schizophrenia
CNS & Neurological Disorders - Drug Targets LPS-induced Murine Neuroinflammation Model: Main Features and Suitability for Pre-clinical Assessment of Nutraceuticals
Current Neuropharmacology Regulatory Triangle of Neurodegeneration, Adult Neurogenesis and MicroRNAs
CNS & Neurological Disorders - Drug Targets Nerve Growth Factor and Brain-Derived Neurotrophic Factor in Schizophrenia and Depression: Findings in Humans, and Animal Models
Current Neuropharmacology Viral Induced Oxidative and Inflammatory Response in Alzheimer’s Disease Pathogenesis with Identification of Potential Drug Candidates: A Systematic Review using Systems Biology Approach
Current Neuropharmacology Astrocyte Pathology in Major Depressive Disorder: Insights from Human Postmortem Brain Tissue
Current Drug Targets The Glial Sodium-Calcium Exchanger: A New Target for Nitric Oxide- Mediated Cellular Toxicity
Current Protein & Peptide Science Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias
Current Neuropharmacology Phytochemicals in the Treatment of Alzheimer’s Disease: A Systematic Review
Current Drug Targets Collective Roles of Molecular Chaperones in Protein Degradation Pathways Associated with Neurodegenerative Diseases
Current Pharmaceutical Biotechnology Small Interfering RNAs and Antisense Oligonucleotides for Treatment of Neurological Diseases
Current Drug Targets Adenosine in the Central Nervous System: Effects on Neurotransmission and Neuroprotection
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Pyroglutamate-Modified Amyloid Beta Peptides: Emerging Targets for Alzheimer´s Disease Immunotherapy
Current Neuropharmacology RNA-Mediated Therapeutics: From Gene Inactivation to Clinical Application
Current Topics in Medicinal Chemistry Subject Index To Volume 1
Recent Patents on CNS Drug Discovery (Discontinued) Mesenchymal Stem Cells: New Approaches for the Treatment of Neurological Diseases
Current Stem Cell Research & Therapy Neurotransmitters and Microglial-Mediated Neuroinflammation
Current Protein & Peptide Science Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer’s Disease in Zebrafish
CNS & Neurological Disorders - Drug Targets Hybrid Molecules Synergistically Acting Against Protein Aggregation Diseases
Current Topics in Medicinal Chemistry Serotonin – Kynurenine Hypothesis of Depression: Historical Overview and Recent Developments
Current Drug Targets