Dopamine D₄ Receptor Antagonists for the Treatment of Cocaine Use Disorders

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.

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