Journal
ADDICTION REVIEWS 2008
Volume 1141, Issue -, Pages 221-232Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1441.015
Keywords
metabotropic glutamate receptors; mGluR5; structure activity relationship; drug addiction; anxiety; depression; FLIPR; cocaine; morphine; nicotine; ethanol; fluorometric Ca2+ flux assay; mGluR5 antagonist; mGluR5 modulator; lead optimization; self-administration; conditioned place preference; Vogel test; tail suspension test; forced swim test
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As a result of intensive investigation, particularly in the pharmaceutical industry, a number of potent and selective metabotropic glutamate receptor subtype 5 (mGluR5) antagonists have been discovered. The structure activity relationship studies that led to the discovery of these mGluR5 antagonists are presented in this review. Results from studies on selected mGluR5 antagonists in animal models that simulate drug reward, reinforcement, and relapse appear promising. The comorbidity between drug abuse and anxiety and depression make drugs active in these disorders of great interest. Clinical studies showed that the mGluR5 antagonist fenobam was an active anxiolytic drug. Several new mGluR5 antagonists produced anxiolytic and antidepressant-like effects in animal models of these disorders. The results from the clinical and animal studies provide information for new approaches to finding mechanistically distinct pharmacotherapies to help patients achieve and maintain abstinence from cocaine, methamphetamine, opiates, ethanol, and nicotine (smoking).
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