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GABAB receptors as a therapeutic strategy in substance use disorders: focus on positive allosteric modulators.

Abstract：

:γ-Aminobutyric acid B (GABAB) receptors and their ligands are postulated as potential therapeutic targets for the treatment of several brain disorders, including drug dependence. Over the past fifteen years positive allosteric modulators (PAMs) have emerged that enhance the effects of GABA at GABAB receptors and which may have therapeutic effects similar to those of agonists but with superior side-effect profiles. This review summarizes current preclinical evidence supporting a role of GABAB receptor PAMs in drug addiction in several paradigms with relevance to reward processes and drug abuse liability. Extensive behavioral research in recent years has indicated that PAMs of GABAB receptors may have a therapeutic efficacy in cocaine, nicotine, amphetamine and alcohol dependence. The magnitude of the effects observed are similar to that of the clinically approved drug baclofen, an agonist at GABAB receptors. Moreover, given that anxiolytic effects are also reported with such ligands they may also benefit in mitigating the withdrawal from drugs of abuse. In summary, a wealth of data now supports the benefits of GABAB receptor PAMs and clinical validation is now warranted.

journal_name

Neuropharmacology

journal_title

Neuropharmacology

authors

Filip M,Frankowska M,Sadakierska-Chudy A,Suder A,Szumiec L,Mierzejewski P,Bienkowski P,Przegaliński E,Cryan JF

doi

10.1016/j.neuropharm.2014.06.016

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

36-47

eissn

0028-3908

issn

1873-7064

pii

S0028-3908(14)00238-X

journal_volume

88

pub_type

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