AUTHOR=Agabio Roberta , Colombo Giancarlo 

TITLE=GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence

JOURNAL=Frontiers in Neuroscience

VOLUME=8

YEAR=2014

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2014.00140

DOI=10.3389/fnins.2014.00140

ISSN=1662-453X

ABSTRACT=<p>The present paper summarizes the preclinical and clinical studies conducted to define the “<italic>anti</italic>-alcohol” pharmacological profile of the prototypic GABA<sub>B</sub> 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 <italic>in vivo</italic> effective ligands, represents a novel, and likely more favorable, option for pharmacological manipulations of the GABA<sub>B</sub> receptor. Accordingly, data collected to date suggest that positive allosteric modulators of the GABA<sub>B</sub> receptor reproduce several “<italic>anti</italic>-alcohol” effects of baclofen and display a higher therapeutic index (with larger separation—in terms of doses—between “<italic>anti</italic>-alcohol” effects and sedation).</p>