title: The preclinical profile of brexpiprazole: what is its clinical relevance for the treatment of psychiatric disorders?
abstract: Brexpiprazole is a serotonin-dopamine activity modulator in clinical development for schizophrenia, adjunctive treatment of major depressive disorder, agitation in Alzheimer's disease and post-traumatic stress disorder. It is a partial agonist at 5-HT1A and D2 receptors with similar potency, and an antagonist at 5-HT2A and adrenergic α1B/2C receptors. Compared with aripiprazole, brexpiprazole is more potent at 5-HT1A receptors and displays less intrinsic activity at D2 receptors. This unique serotonin and dopamine modulatory activity has shown robust antipsychotic, antidepressant-like and anxiolytic activities, and limited extrapyramidal symptom liability with pro-cognitive efficacy in animal models. Phase III clinical trials have been successfully completed in schizophrenia and adjunctive use in major depressive disorder, with the US FDA approval obtained for these uses; Phase III studies in Alzheimer's disease and post-traumatic stress disorder are ongoing.
authors.affiliation: a 1 New York Medical College, Valhalla, New York, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Citrome
authors.affiliation: b 2 Discovery Pharmacology Research, H. Lundbeck, Copenhagen-Valby, Denmark.
authors.forename: Tine Bryan
authors.initials: TB
authors.lastname: Stensbøl
authors.affiliation: c 3 Qs' Research Institute, Otsuka Pharmaceutical Co., Ltd. Tokushima, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Maeda
mesh_terms: D000818:Animals; D017326:Clinical Trials, Phase III as Topic; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D001523:Mental Disorders / Q000188:drug therapy*; D015363:Quinolones / Q000494:pharmacology* / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D013876:Thiophenes / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D015363:Quinolones; D013876:Thiophenes; C000591922:brexpiprazole
keywords: behavioral models; pharmacology; preclinical; receptor binding; • brexpiprazole