title: GABAB receptor ligands for the treatment of alcohol use disorder: preclinical and clinical evidence.
abstract: 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).
authors.affiliation: Department of Biomedical Sciences, University of Cagliari Monserrato, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Agabio
authors.affiliation: Section of Cagliari, Neuroscience Institute, National Research Council of Italy Monserrato, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
keywords: GABAB receptor; alcohol use disorder; animal models of alcohol use disorder; baclofen; positive allosteric modulators