title: Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach.
abstract: BACKGROUND
  Neuropharmacology research in glutamate-modulating drugs supports their development and use in the management of neuropsychiatric disorders, including major depression, Alzheimer's disorder and schizophrenia. Concomitantly, there is a growing use of these agents used in the treatment of obsessive-compulsive disorder (OCD).
  
  
  METHODS
  This article provides a review of glutamate-modulating drugs used in the treatment of OCD. Specifically, the authors examine riluzole, N-acetylcysteine, d-cycloserine, glycine, ketamine, memantine and acamprosate as treatments. Furthermore, recent genetic epidemiology research findings are presented with a focus on the positional candidate genes SLC1A1 (a glutamate transporter), ADAR3 (an RNA-editing enzyme), RYR3 (a Ca(2+) channel), PBX1 (a homeobox transcription factor) and a GWAS candidate gene, DLGAP1 (a protein interacting with post-synaptic density). These genetic findings are submitted to a curated bioinformatics database to conform a biological network for discerning potential pharmacological targets.
  
  
  CONCLUSIONS
  In the genetically informed network, known genes and identified key connecting components, including DLG4 (a developmental gene), PSD-95 (a synaptic scaffolding protein) and PSEN1 (presenilin, a regulator of secretase), conform a group of potential pharmacological targets. These potential targets can be explored, in the future, to deliver new therapeutic approaches to OCD. There is also the need to develop a better understanding of neuroprotective mechanisms as a foundation for future OCD drug discovery.
authors.affiliation: Johns Hopkins University School of Medicine , 1800 Orleans St. - 12th floor, Baltimore, MD 21287 , USA +1 443 287 2291 ; +1 410 955 8691 ; mjgrados@jhmi.edu.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Grados
authors.forename: Matt W
authors.initials: MW
authors.lastname: Specht
authors.forename: Hyung-Mo
authors.initials: HM
authors.lastname: Sung
authors.forename: Diandra
authors.initials: D
authors.lastname: Fortune
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009771:Obsessive-Compulsive Disorder / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism
chemical_list: D018698:Glutamic Acid