Abstract
Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been reported. While COMT inhibition may be beneficial in a number of disease states, most of the effort over the years has been directed at boosting L-DOPA concentrations as adjunct treatment for Parkinson’s disease. This review summarizes the major classes of COMT inhibitors, from early catechol and pyrogallol variants to bisubstrate inhibitors. The nitrocatechol substructure has proven to be a particularly productive scaffold, resulting in two marketed drugs and several improved drug candidates working their way through clinical trials.
Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinson's disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, DOPAC
CNS & Neurological Disorders - Drug Targets
Title:Inhibitors of Catechol-O-Methyltransferase
Volume: 11 Issue: 3
Author(s): James C. Barrow
Affiliation:
Keywords: Catechol-O-methyltransferase, COMT, dopamine, L-DOPA, Parkinson's disease, nitrocatechol, MB-COMT, SAM Binding, HPLC, DOPAC
Abstract: Since the identification of Catechol-O-Methyltransferase (COMT) by Axelrod in 1957, many inhibitors of this enzyme have been reported. While COMT inhibition may be beneficial in a number of disease states, most of the effort over the years has been directed at boosting L-DOPA concentrations as adjunct treatment for Parkinson’s disease. This review summarizes the major classes of COMT inhibitors, from early catechol and pyrogallol variants to bisubstrate inhibitors. The nitrocatechol substructure has proven to be a particularly productive scaffold, resulting in two marketed drugs and several improved drug candidates working their way through clinical trials.
Export Options
About this article
Cite this article as:
C. Barrow James, Inhibitors of Catechol-O-Methyltransferase, CNS & Neurological Disorders - Drug Targets 2012; 11 (3) . https://dx.doi.org/10.2174/187152712800672517
DOI https://dx.doi.org/10.2174/187152712800672517 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
- 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 Role of Brain Gaseous Transmitters in the Regulation of the Circulatory System
Current Pharmaceutical Biotechnology Targeting Ras Activity Prevented Amyloid Beta-Induced Aberrant Neuronal Cell Cycle Re-Entry and Death
Current Alzheimer Research Natural Thiazoline-Based Cyclodepsipeptides from Marine Cyanobacteria: Chemistry, Bioefficiency and Clinical Aspects
Current Medicinal Chemistry Micro-Nanomaterials for Tumor Microwave Hyperthermia: Design, Preparation, and Application
Current Drug Delivery Scorpion Toxin-potassium Channel Interaction Law and its Applications
Venoms and Toxins Recent Advances on the Roles of NO in Cancer and Chronic Inflammatory Disorders
Current Medicinal Chemistry Possible Neuroprotective Strategies for Huntingtons Disease
Current Neuropharmacology Effect of Phosphorylation and Aggregation on Tau Binding to Dna
Protein & Peptide Letters Neuroimmune Aspects of Sjogren`s Syndrome: Role of VIP/VPAC System in Immune and Salivary Gland Epithelial Cell Function
Current Pharmaceutical Design Histone Deacetylase Inhibitors: A New Wave of Molecular Targeted Anticancer Agents
Recent Patents on Anti-Cancer Drug Discovery Synthesis of Some Coumarinyl Chalcones and their Antiproliferative Activity Against Breast Cancer Cell Lines
Letters in Drug Design & Discovery Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Liposome-linear polyethyleneimine-DNA Nanocomplexes for Gene Delivery: Preparation, Characterization and In Vitro Transfection Activity
Current Nanoscience Redox Chemistry of Green Tea Polyphenols: Therapeutic Benefits in Neurodegenerative Diseases
Mini-Reviews in Medicinal Chemistry Recent Advances in Antabuse (Disulfiram): The Importance of its Metal-binding Ability to its Anticancer Activity
Current Medicinal Chemistry Iron Chelators as Potential Therapeutic Agents for Parkinsons Disease
Current Bioactive Compounds HDAC Inhibitors as Novel Anti-Cancer Therapeutics
Recent Patents on Anti-Cancer Drug Discovery Importance of Wnt Signaling in the Tumor Stroma Microenvironment
Current Cancer Drug Targets Glycosylated Antitumor Ether Lipids: Activity and Mechanism of Action
Anti-Cancer Agents in Medicinal Chemistry Agonist-Trafficking and Hallucinogens
Current Medicinal Chemistry