A computational network analysis based on targets of antipsychotic agents

Abstract

Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI network with 77 significantly interconnected target genes was generated. By historeceptomics analysis, significant brain region specific target-drug interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in caudate nucleus and pons (P-value<0.005), DRD2-Bifeprunox in caudate nucleus and pituitary (P-value<0.0005), DRD4-Loxapine in Pineal (P-value<0.00001)) and 5-hydroxytryptamine receptor (HTR2A-Risperidone in occipital lobe, prefrontal cortex and subthalamic nucleus (P-value<0.0001)). By pathway grouped network analysis, 34 significant pathways were identified and significantly grouped into 6 sub networks related with drug metabolism, Calcium signaling, GABA receptors, dopamine receptors, Bile secretion and Gap junction. Our results may provide biological explanation for antipsychotic targets and insights for molecular mechanism of antipsychotic agents.

Keywords: Antipsychotic agents; Historeceptomics; Network; Pathway; Targets.