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Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles

Abstract

Atypical antipsychotic drugs offer several notable benefits over typical antipsychotics, including greater improvement in negative symptoms, cognitive function, prevention of deterioration, and quality of life, and fewer extrapyramidal symptoms (EPS). However, concerns about EPS have been replaced by concerns about other side effects, such as weight gain, glucose dysregulation and dyslipidemia. These side effects are associated with potential long-term cardiovascular health risks, decreased medication adherence, and may eventually lead to clinical deterioration. Despite a greater understanding of the biochemical effects of these drugs in recent years, the pharmacological mechanisms underlying their various therapeutic properties and related side effects remain unclear. Besides dopamine D2 receptor antagonism, a characteristic feature of all atypical antipsychotic drugs, these agents also bind to a range of non-dopaminergic targets, including serotonin, glutamate, histamine, α-adrenergic and muscarinic receptors. This review examines the potential contribution of different receptors to metabolic side effects associated with atypical antipsychotic treatment for all seven agents currently marketed in the United States (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole, paliperidone and clozapine) and another agent (bifeprunox) in clinical development at the time of this publication.

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Acknowledgements

This study has been financially supported by Solvay Pharmaceuticals, Marietta Georgia and Wyeth Research, Collegeville Pennsylvania. Chris Gutteridge and Alyce Erdekian of Centron provided editorial support for this manuscript.

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Nasrallah, H. Atypical antipsychotic-induced metabolic side effects: insights from receptor-binding profiles. Mol Psychiatry 13, 27–35 (2008). https://doi.org/10.1038/sj.mp.4002066

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