title: 50 years of hurdles and hope in anxiolytic drug discovery.
abstract: Anxiety disorders are the most prevalent group of psychiatric diseases, and have high personal and societal costs. The search for novel pharmacological treatments for these conditions is driven by the growing medical need to improve on the effectiveness and the side effect profile of existing drugs. A huge volume of data has been generated by anxiolytic drug discovery studies, which has led to the progression of numerous new molecules into clinical trials. However, the clinical outcome of these efforts has been disappointing, as promising results with novel agents in rodent studies have very rarely translated into effectiveness in humans. Here, we analyse the major trends from preclinical studies over the past 50 years conducted in the search for new drugs beyond those that target the prototypical anxiety-associated GABA (γ-aminobutyric acid)-benzodiazepine system, which have focused most intensively on the serotonin, neuropeptide, glutamate and endocannabinoid systems. We highlight various key issues that may have hampered progress in the field, and offer recommendations for how anxiolytic drug discovery can be more effective in the future.
authors.affiliation: Sanofi, Exploratory Unit, Chilly-Mazarin 91385, France.
authors.forename: Guy
authors.initials: G
authors.lastname: Griebel
authors.forename: Andrew
authors.initials: A
authors.lastname: Holmes
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D002986:Clinical Trials as Topic; D004195:Disease Models, Animal; D015195:Drug Design; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D058990:Molecular Targeted Therapy
chemical_list: D014151:Anti-Anxiety Agents