title: Identifying Medication Targets for Psychostimulant Addiction: Unraveling the Dopamine D3 Receptor Hypothesis.
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.
authors.affiliation: †Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, Maryland 21224, United States.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Keck
authors.affiliation: §Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157-1083, United States.
authors.forename: William S
authors.initials: WS
authors.lastname: John
authors.affiliation: §Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157-1083, United States.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Czoty
authors.affiliation: §Department of Physiology and Pharmacology, Wake Forest School of Medicine, Winston-Salem, North Carolina 27157-1083, United States.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nader
authors.affiliation: †Medicinal Chemistry Section, Molecular Targets and Medications Discovery Branch, National Institute on Drug Abuse-Intramural Research Program, National Institutes of Health, 333 Cassell Drive, Baltimore, Maryland 21224, United States.
authors.forename: Amy Hauck
authors.initials: AH
authors.lastname: Newman
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D055808:Drug Discovery; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D050637:Receptors, Dopamine D3 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D019966:Substance-Related Disorders / Q000188:drug therapy*
chemical_list: D000697:Central Nervous System Stimulants; D050637:Receptors, Dopamine D3
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