title: Network-assisted investigation of antipsychotic drugs and their targets.
abstract: Antipsychotic drugs are tranquilizing psychiatric medications primarily used in the treatment of schizophrenia and similar severe mental disorders. So far, most of these drugs have been discovered without knowing much on the molecular mechanisms of their actions. The available large amount of pharmacogenetics, pharmacometabolomics, and pharmacoproteomics data for many drugs makes it possible to systematically explore the molecular mechanisms underlying drug actions. In this study, we applied a unique network-based approach to investigate antipsychotic drugs and their targets. We first retrieved 43 antipsychotic drugs, 42 unique target genes, and 46 adverse drug interactions from the DrugBank database and then generated a drug-gene network and a drug-drug interaction network. Through drug-gene network analysis, we found that seven atypical antipsychotic drugs tended to form two clusters that could be defined by drugs with different target receptor profiles. In the drug-drug interaction network, we found that three drugs (zuclopenthixol, ziprasidone, and thiothixene) tended to have more adverse drug interactions than others, while clozapine had fewer adverse drug interactions. This investigation indicated that these antipsychotics might have different molecular mechanisms underlying the drug actions. This pilot network-assisted investigation of antipsychotics demonstrates that network-based analysis is useful for uncovering the molecular actions of antipsychotics.
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA.
authors.forename: Jingchun
authors.initials: J
authors.lastname: Sun
authors.forename: Hua
authors.initials: H
authors.lastname: Xu
authors.forename: Zhongming
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D014150:Antipsychotic Agents / Q000378:metabolism* / Q000627:therapeutic use; D003006:Clopenthixol / Q000378:metabolism / Q000627:therapeutic use; D016208:Databases, Factual; D004347:Drug Interactions; D053263:Gene Regulatory Networks; D006801:Humans; D010879:Piperazines / Q000378:metabolism / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy; D013844:Thiazoles / Q000378:metabolism / Q000627:therapeutic use; D013888:Thiothixene / Q000378:metabolism / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D013888:Thiothixene; D003006:Clopenthixol