Molecular mechanisms of olanzapine against agitation in schizophrenia and bipolar disorder based on network pharmacology and molecular docking.

Olanzapine, a second-generation antipsychotic, is commonly used to manage agitation in patients with schizophrenia and bipolar disorder, though its underlying mechanism of action remains unclear. In this study, network pharmacology and molecular docking were applied to explore the potential molecular mechanisms of olanzapine. Targets related to olanzapine were retrieved from GeneCards, SwissTargetPrediction, and the Comparative Toxicogenomics Database (CTD), while disease-associated targets were collected from DisGeNET and GeneCards. A protein-protein interaction (PPI) network was constructed to identify key targets. Functional enrichment analyses using the Database for Annotation, Visualization and Integrated Discovery (DAVID) and Bioinformatics platforms indicated involvement in cell proliferation, apoptosis, and inflammation. The core targets identified included brain-derived neurotrophic factor (BDNF), insulin (INS), AKT serine/threonine kinase 1 (AKT1), tumor protein p53 (TP53), insulin-like growth factor 1 (IGF1), nerve growth factor (NGF), nuclear factor kappa B subunit 1 (NFKB1), and fibroblast growth factor 2 (FGF2). These targets are primarily involved in the phosphoinositide 3-kinase (PI3K)-AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Molecular docking demonstrated strong binding affinities between olanzapine and these targets, with docking scores ranging from - 5.3 to - 8.8 kilocalories per mole (kcal/mol). These findings suggest that olanzapine, as an antipsychotic, may alleviate acute agitation symptoms by modulating signaling pathways associated with neuroinflammation and neuroplasticity, providing a basis for further research into its mechanism of action in neuropsychiatric disorders.