Abstract
L-DOPA is a di-hydroxy-phenyl, catecholamine precursor, amino acid, initially considered as an inert compound and now the key stone for the treatment of Parkinsons disease (PD) and some hereditary dystonias. L-DOPA, when administered to mammals, is rapidly metabolized to dopamine and 3-OM-DOPA, and its half-life in plasma is roughly 2 hours which has been considered the explanation for some of the L-DOPA related complications in PD. There have been, therefore, sophisticated methods of improving its pharmacokinetics by the association of decarboxylase and COMT inhibitors, slow release preparations and continuous infusions. In addition to its symptomatic effects, the impact of L-DOPA on the natural course of the disease is intriguing. By alleviating motor deficits, L-DOPA may improve health quality and life span in patients with PD, but there are neurotoxic and neurotrophic effects of L-DOPA which may produce long term effects on disease progression. These effects are dependent of the dose, the status of the metabolic pathways involved in catecholamine metabolism, the balance of free radicals and their scavengers and the function of glia. Finally, there is new data suggesting that L-DOPA may be not only a catecholamine precursor but also a neurotransmitter by itself of yet unknown function.
Keywords: Dopamine neurons, glial cells, glutathione, apoptosis, MAP kinase, L-DOPA-responsive dystonia, Parkinson's disease, parkin gene
Current Topics in Medicinal Chemistry
Title: Half a Century of l-DOPA
Volume: 9 Issue: 10
Author(s): Maria Angeles Mena, Maria Jose Casarejos, Rosa Maria Solano and Justo Garcia de Yebenes
Affiliation:
Keywords: Dopamine neurons, glial cells, glutathione, apoptosis, MAP kinase, L-DOPA-responsive dystonia, Parkinson's disease, parkin gene
Abstract: L-DOPA is a di-hydroxy-phenyl, catecholamine precursor, amino acid, initially considered as an inert compound and now the key stone for the treatment of Parkinsons disease (PD) and some hereditary dystonias. L-DOPA, when administered to mammals, is rapidly metabolized to dopamine and 3-OM-DOPA, and its half-life in plasma is roughly 2 hours which has been considered the explanation for some of the L-DOPA related complications in PD. There have been, therefore, sophisticated methods of improving its pharmacokinetics by the association of decarboxylase and COMT inhibitors, slow release preparations and continuous infusions. In addition to its symptomatic effects, the impact of L-DOPA on the natural course of the disease is intriguing. By alleviating motor deficits, L-DOPA may improve health quality and life span in patients with PD, but there are neurotoxic and neurotrophic effects of L-DOPA which may produce long term effects on disease progression. These effects are dependent of the dose, the status of the metabolic pathways involved in catecholamine metabolism, the balance of free radicals and their scavengers and the function of glia. Finally, there is new data suggesting that L-DOPA may be not only a catecholamine precursor but also a neurotransmitter by itself of yet unknown function.
Export Options
About this article
Cite this article as:
Mena Angeles Maria, Casarejos Jose Maria, Solano Maria Rosa and de Yebenes Garcia Justo, Half a Century of l-DOPA, Current Topics in Medicinal Chemistry 2009; 9 (10) . https://dx.doi.org/10.2174/156802609789378263
DOI https://dx.doi.org/10.2174/156802609789378263 |
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
-
G Protein-Coupled Receptor Signaling Complexity in Neuronal Tissue:Implications for Novel Therapeutics
Current Alzheimer Research Altering the Tropism of Lentiviral Vectors through Pseudotyping
Current Gene Therapy Autophagy as a Molecular Target of Flavonoids Underlying their Protective Effects in Human Disease
Current Medicinal Chemistry Complement and Microglia in the Neuropathogenesis of HIV Infection: Pro- and Anti-Inflammatory Aspects
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Targeted Therapy of the Insulin-Like Growth Factor-1 Receptor in Cancer
Combinatorial Chemistry & High Throughput Screening Sphingolipids as Emerging Drug Targets: Therapeutic Applications of Ceramide Analogs
Drug Design Reviews - Online (Discontinued) Mitochondria-Targeting Anticancer Metal Complexes
Current Medicinal Chemistry Kinetic Study on the Effects of Extremely Low Frequency Electromagnetic Field on Catalase, Cytochrome P450 and Inducible Nitric Oxide Synthase in Human HaCaT and THP-1 Cell Lines
CNS & Neurological Disorders - Drug Targets Curcumin, Resveratrol and Cannabidiol as Natural Key Prototypes in Drug Design for Neuroprotective Agents
Current Neuropharmacology Small-molecule Modulation of HDAC6 Activity: The Propitious Therapeutic Strategy to Vanquish Neurodegenerative Disorders
Current Medicinal Chemistry Gene and Cancer Therapy - Pseudorabies Virus: A Novel Research and Therapeutic Tool?
Current Gene Therapy Molecular Mechanisms of Action of Gas1 and its Possible Therapeutic Applications
Current Signal Transduction Therapy The Need for Calcium Channels in Cell Proliferation
Recent Patents on Anti-Cancer Drug Discovery Malignant Mesothelioma: Cell Survival Pathways and Radiation Therapy
Current Respiratory Medicine Reviews VIP in Inflammatory Bowel Disease: State of the Art
Endocrine, Metabolic & Immune Disorders - Drug Targets Individualized Treatment Planning in Oncology: Role of PET and Radiolabelled Anticancer Drugs in Predicting Tumour Resistance
Current Pharmaceutical Design Neuronal Membranes are Key to the Pathogenesis of Alzheimers Disease: the Role of Both Raft and Non-Raft Membrane Domains
Current Alzheimer Research Biomarkers
Current Pharmaceutical Design The Gene Expression Profiles of Medulloblastoma Cell Lines Resistant to Preactivated Cyclophosphamide
Current Cancer Drug Targets Hormetic Potential of Sulforaphane (SFN) in Switching Cells’ Fate Towards Survival or Death
Mini-Reviews in Medicinal Chemistry