Antagonists at metabotropic glutamate receptor subtype 5: structure activity relationships and therapeutic potential for addiction.

Abstract:

: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).

journal_name

Ann N Y Acad Sci

authors

Carroll FI

doi

10.1196/annals.1441.015

subject

Has Abstract

pub_date

2008-10-01 00:00:00

pages

221-32

eissn

0077-8923

issn

1749-6632

pii

NYAS1141015

journal_volume

1141

pub_type

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