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
-
Editorial [Hot Topic:Therapeutic Potential of Peptide Motifs - Part V (Executive Guest Editor: Jean-Claude Herve)]
Current Pharmaceutical Design A Randomized, Double-Blind, Placebo-Controlled, 16-Week Study of the H<sub>3</sub> Receptor Antagonist, GSK239512 as a Monotherapy in Subjects with Mild-to-Moderate Alzheimer’s Disease
Current Alzheimer Research The Effect of Resveratrol on Neurodegenerative Disorders: Possible Protective Actions Against Autophagy, Apoptosis, Inflammation and Oxidative Stress
Current Pharmaceutical Design Antioxidants and Neuroprotection in the Adult and Developing Central Nervous System
Current Medicinal Chemistry Role of Methylene Blue in Trauma Neuroprotection and Neuropsychiatric Diseases
CNS & Neurological Disorders - Drug Targets Psychomotor Seizure Test, Neurotoxicity and in vitro Neuroprotection Assay of some Semicarbazone Analogues
Central Nervous System Agents in Medicinal Chemistry Nicotinamide Adenine Dinucleotide Based Therapeutics
Current Medicinal Chemistry Minocycline Mediated Mitochondrial Cytoprotection: Premises for Therapy of Cerebrovascular and Neurodegenerative Diseases
Current Drug Targets Glutamate Receptors in Human Caudate Nucleus in Normal Aging and Alzheimer’s Disease
Current Alzheimer Research Autophagy: A Major Target of Cadmium Nephrotoxicity
Current Chemical Biology The Use of Stem Cells in Regenerative Medicine for Parkinson’s and Huntington’s Diseases
Current Medicinal Chemistry Current and Future Therapeutic Strategies for Parkinsons Disease
Current Pharmaceutical Design Shutting Down the Furnace: Preferential Killing of Cancer Cells with Mitochondrial-Targeting Molecules
Current Medicinal Chemistry Histone Deacetylase (HDAC) Inhibitors - emerging roles in neuronal memory, learning, synaptic plasticity and neural regeneration
Current Neuropharmacology Role of Insulin Signaling in the Interaction Between Alzheimer Disease and Diabetes Mellitus: A Missing Link to Therapeutic Potential
Current Aging Science Association of Apolipoprotein E (ApoE) Polymorphism with Alzheimer's Disease in Chinese Population
Current Alzheimer Research Neural Stem Cells: From Neurobiology to Clinical Applications
Current Pharmaceutical Biotechnology Modelling and Treating Amyotrophic Lateral Sclerosis through Induced- Pluripotent Stem Cells Technology
Current Stem Cell Research & Therapy Natural Compounds and Plant Extracts as Therapeutics Against Chronic Inflammation in Alzheimer's Disease - A Translational Perspective
CNS & Neurological Disorders - Drug Targets The Ubiquitous Choline Transporter SLC44A1
Central Nervous System Agents in Medicinal Chemistry