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GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence
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GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence
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Journal Article
GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence
2014
Overview
The present paper summarizes the preclinical and clinical studies conducted to define the \"anti-alcohol\" pharmacological profile of the prototypic GABAB receptor agonist, baclofen, and its therapeutic potential for treatment of alcohol use disorder (AUD). Numerous studies have reported baclofen-induced suppression of alcohol drinking (including relapse- and binge-like drinking) and alcohol reinforcing, motivational, stimulating, and rewarding properties in rodents and monkeys. The majority of clinical surveys conducted to date-including case reports, retrospective chart reviews, and randomized placebo-controlled studies-suggest the ability of baclofen to suppress alcohol consumption, craving for alcohol, and alcohol withdrawal symptomatology in alcohol-dependent patients. The recent identification of a positive allosteric modulatory binding site, together with the synthesis of in vivo effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABAB receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABAB receptor reproduce several \"anti-alcohol\" effects of baclofen and display a higher therapeutic index (with larger separation-in terms of doses-between \"anti-alcohol\" effects and sedation).
Publisher
Frontiers Research Foundation,Frontiers Media S.A
