Abstract
The identification of effective medications for the management of cocaine use disorders remains an unmet public health challenge. In view of the prominent role of dopaminergic mechanisms in cocaine’s abuse-related effects, research has focused on the development of subtype-selective dopamine D1-4 receptor antagonists. Here, we briefly recap the current status of this research effort, with a focus on several aspects of D4 research that may be pertinent to the consideration of D4 ligands in the development of candidate medications. Additionally, we present data from selfadministration studies in nonhuman primates showing that intravenous cocaine-maintained behavior is moderately, though non-significantly, decreased by doses of the D4-selective partial agonist Ro10-5824 and dramatically reduced by the D4- selective receptor antagonist NGD-94-1. The effects of these D4 ligands on cocaine self-administration were consistent among subjects and occurred in the absence of comparable effects on food-maintained responding. These data suggest that available D4 receptor antagonists should be investigated further as candidate medications for the management of cocaine use disorders.
Keywords: Cocaine use disorders, dopamine D4 receptor antagonists, L-745, 870 (3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1Hpyrrolo[ 2, 3-b]pyridine, NGD-94-1 ( 2-[4-[(2-Phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]-pyrimidine), Nonhuman primates, Ro10-5824 (2-methyl-5-[(4-phenyl-3, 6-dihydro-2H-pyridin-1-yl)methyl]pyrimidin-4-amine), Self-administration.
CNS & Neurological Disorders - Drug Targets
Title:Dopamine D4 Receptor Antagonists for the Treatment of Cocaine Use Disorders
Volume: 14 Issue: 6
Author(s): Jack Bergman and Curtis G. Rheingold
Affiliation:
Keywords: Cocaine use disorders, dopamine D4 receptor antagonists, L-745, 870 (3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1Hpyrrolo[ 2, 3-b]pyridine, NGD-94-1 ( 2-[4-[(2-Phenyl-1H-imidazol-5-yl)methyl]-1-piperazinyl]-pyrimidine), Nonhuman primates, Ro10-5824 (2-methyl-5-[(4-phenyl-3, 6-dihydro-2H-pyridin-1-yl)methyl]pyrimidin-4-amine), Self-administration.
Abstract: The identification of effective medications for the management of cocaine use disorders remains an unmet public health challenge. In view of the prominent role of dopaminergic mechanisms in cocaine’s abuse-related effects, research has focused on the development of subtype-selective dopamine D1-4 receptor antagonists. Here, we briefly recap the current status of this research effort, with a focus on several aspects of D4 research that may be pertinent to the consideration of D4 ligands in the development of candidate medications. Additionally, we present data from selfadministration studies in nonhuman primates showing that intravenous cocaine-maintained behavior is moderately, though non-significantly, decreased by doses of the D4-selective partial agonist Ro10-5824 and dramatically reduced by the D4- selective receptor antagonist NGD-94-1. The effects of these D4 ligands on cocaine self-administration were consistent among subjects and occurred in the absence of comparable effects on food-maintained responding. These data suggest that available D4 receptor antagonists should be investigated further as candidate medications for the management of cocaine use disorders.
Export Options
About this article
Cite this article as:
Bergman Jack and Rheingold G. Curtis, Dopamine D4 Receptor Antagonists for the Treatment of Cocaine Use Disorders, CNS & Neurological Disorders - Drug Targets 2015; 14 (6) . https://dx.doi.org/10.2174/1871527314666150529132723
DOI https://dx.doi.org/10.2174/1871527314666150529132723 |
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
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
-
Resveratrol: A Multifunctional Cytoprotective Molecule
Current Pharmaceutical Biotechnology On the Sympathetic Innervation of the Human Greater Saphenous Vein: Relevance to Clinical Practice
Current Vascular Pharmacology L-Carnitine - Metabolic Functions and Meaning in Humans Life
Current Drug Metabolism Effect of Cabergoline on Cognitive Impairments in Transgenic <i>Drosophila</i> Model of Parkinson’s Disease
Letters in Drug Design & Discovery Design, Synthesis, Crystal Structure, Fluorescence, Molecular Docking and DFT Studies of 3,6-Dinitro-N-octylcarbazole
Current Organic Chemistry Update on Pharmacological Treatment of Progressive Myoclonus Epilepsies
Current Pharmaceutical Design Functional Human 5-HT6 Receptor Assay for High Throughput Screening of Chemical Ligands and Binding Proteins
Combinatorial Chemistry & High Throughput Screening Application of Human Laboratory Models to Pharmacotherapy Development for Alcohol Dependence
Current Pharmaceutical Design Chalcone Derivatives Activate and Desensitize the Transient Receptor Potential Ankyrin 1 Cation Channel, Subfamily A, Member 1 TRPA1 Ion Channel: Structure-Activity Relationships in vitro and Anti-Nociceptive and Anti-inflammatory Activity in vivo
CNS & Neurological Disorders - Drug Targets Immunomodulation in Multiple Sclerosis by Phytotherapy
Current Immunology Reviews (Discontinued) Cholinergic Targets in Lung Cancer
Current Pharmaceutical Design Clinical and Serological Biomarkers of Treatment’s Response in Multiple Sclerosis Patients Treated Continuously with Interferonβ-1b for More than a Decade
CNS & Neurological Disorders - Drug Targets Progress on Multi-Modality Molecular Imaging
Current Medical Imaging New Perspectives in Glioma Immunotherapy
Current Pharmaceutical Design Different Concepts of Drug Delivery in Disease Entities
Mini-Reviews in Medicinal Chemistry Organotypic Hippocampal Slice Cultures for Studies of Brain Damage, Neuroprotection and Neurorepair
Current Drug Targets - CNS & Neurological Disorders Detailed Molecular Surveillance of the HIV-1 Outbreak Among People who Inject Drugs (PWID) in Athens During a Period of Four Years
Current HIV Research Targeting the Toll-System in Cardiovascular Sciences
Recent Patents on Inflammation & Allergy Drug Discovery The Role of Intranasal Oxytocin in the Treatment of Patients with Schizophrenia: A Systematic Review
CNS & Neurological Disorders - Drug Targets Homocysteine and Hyperhomocysteinaemia
Current Medicinal Chemistry