Metabolic effects of atypical antipsychotics: molecular targets

Abstract

Atypical antipsychotics (AAPs) are commonly prescribed drugs for treating schizophrenia, bipolar disorder and other mental diseases characterized by psychotic features. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with relevant metabolic side effects - the so-called metabolic syndrome (MetS) - which is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which increase the risk for development of type 2 diabetes (T2D) and cardiovascular disease. In this review, we will describe the molecular and cellular mechanisms involved in the metabolic effects of AAPs. These mechanisms are complex, as AAPs target many receptors and other proteins, and significantly affect the activities of many hormones and neuromodulators. Additionally, these mechanisms involve practically all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better knowledge of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinical differences among AAPs is necessary in order to develop novel AAPs with less adverse effects, and to develop adjuvant therapies to patients receiving antipsychotic medication.