title: The preclinical discovery and development of quetiapine for the treatment of mania and depression.
abstract: Bipolar disorder is a chronic disabling condition characterized by alternating manic and depressive episodes. Bipolar disorder has been associated with functional impairment, poor quality of life, morbidity and mortality. Despite its significant clinical, social and economic burden, treatment options for bipolar disorder are still limited. Several clinical trials have shown efficacy of the atypical antipsychotic quetiapine (QTP) in the treatment of this condition. However, the mechanisms underlying the antidepressant and anti-manic effects of QTP remain poorly understood. Areas covered: The article provides the emerging evidence from pre-clinical studies regarding the antidepressant and anti-manic mechanisms of action of QTP. In combination with its primary active metabolite norquetiapine, QTP modulates several neurotransmitter systems, including serotonin, dopamine, noradrenaline and histamine. QTP also seems to influence mediators of the immune system. Expert opinion: Pre-clinical studies have provided valuable information on the potential antidepressant mechanisms of action of QTP, but pre-clinical studies on QTP's anti-manic effects are still scarce. A major problem refers to the lack of valid experimental models for bipolar disorder. Additionally, immune and genetic based studies are largely descriptive. The role of the QTP metabolite norquetiapine in modulating non-neurotransmitter systems also needs to be further addressed.
authors.affiliation: a Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina , Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.|b Laboratório de Neurobiologia, Departamento de Morfologia, Instituto de Ciências Biológicas , Universidade Federal de Minas Gerais , Belo Horizonte , Brasil.
authors.forename: Aline Silva de
authors.initials: AS
authors.lastname: Miranda
authors.affiliation: c Laboratório de Neuropsicofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas , Universidade Federal de Minas Gerais , Belo Horizonte , Brasil.
authors.forename: Fabrício A
authors.initials: FA
authors.lastname: Moreira
authors.affiliation: a Laboratório Interdisciplinar de Investigação Médica, Faculdade de Medicina , Universidade Federal de Minas Gerais , Belo Horizonte , Brazil.|d Neuropsychiatry Program, Department of Psychiatry & Behavioral Sciences, McGovern Medical School , University of Texas Health Science Center at Houston , Houston , TX , USA.
authors.forename: Antônio Lúcio
authors.initials: AL
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy* / Q000503:physiopathology; D003987:Dibenzothiazepines / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical; D006801:Humans; D011788:Quality of Life; D000069348:Quetiapine Fumarate / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate; C572724:norquetiapine
keywords: BDNF; Quetiapine; bipolar depression; bipolar disorder; clock genes; dopamine; mania; norquetiapine; serotonin