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.
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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 |
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