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.
journal_name
J Med Chemjournal_title
Journal of medicinal chemistryauthors
Keck TM,John WS,Czoty PW,Nader MA,Newman AHdoi
10.1021/jm501512bsubject
Has Abstractpub_date
2015-07-23 00:00:00pages
5361-80issue
14eissn
0022-2623issn
1520-4804journal_volume
58pub_type
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