Glutamate drugs and pharmacogenetics of OCD: a pathway-based exploratory approach

• Published in: Expert opinion on drug discovery Vol. 8; no. 12; p. 1515
• Main Authors: Grados, Marco A, Specht, Matt W, Sung, Hyung-Mo, Fortune, Diandra
• Format: Journal Article
• Language: English
• Published: England 01-12-2013
• Subjects: Animals; Central Nervous System - metabolism; Glutamic Acid - metabolism; Humans; Obsessive-Compulsive Disorder - drug therapy; Obsessive-Compulsive Disorder - genetics; Obsessive-Compulsive Disorder - metabolism
• ISSN: 1746-045X
• DOI: 10.1517/17460441.2013.845553

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).
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.
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.