Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis

Thomas M. Keck, William S. John, Paul W. Czoty, Michael A. Nader, Amy Hauck Newman

    Research output: Contribution to journalArticlepeer-review

    61 Scopus citations

    Abstract

    The dopamine D3 receptor (D3R) is a target for developing medications to treat substance use disorders. D3R-selective compounds with high affinity and varying efficacies have been discovered, providing critical research tools for cell-based studies that have been translated to in vivo models of drug abuse. D3R antagonists and partial agonists have shown especially promising results in rodent models of relapse-like behavior, including stress-, drug-, and cue-induced reinstatement of drug seeking. However, to date, translation to human studies has been limited. Herein, we present an overview and illustrate some of the pitfalls and challenges of developing novel D3R-selective compounds toward clinical utility, especially for treatment of cocaine abuse. Future research and development of D3R-selective antagonists and partial agonists for substance abuse remains critically important but will also require further evaluation and development of translational animal models to determine the best time in the addiction cycle to target D3Rs for optimal therapeutic efficacy.

    Original languageEnglish (US)
    Pages (from-to)5361-5380
    Number of pages20
    JournalJournal of Medicinal Chemistry
    Volume58
    Issue number14
    DOIs
    StatePublished - Jul 23 2015

    All Science Journal Classification (ASJC) codes

    • Molecular Medicine
    • Drug Discovery

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