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Can sodium/hydrogen exchange inhibitors be repositioned for treating attention deficit hyperactivity disorder? An in silico approach.

Authors
  • Faraone, Stephen V
  • Zhang-James, Yanli
Type
Published Article
Journal
American Journal of Medical Genetics Part B Neuropsychiatric Genetics
Publisher
Wiley (John Wiley & Sons)
Publication Date
Oct 01, 2013
Volume
162B
Issue
7
Pages
711–717
Identifiers
DOI: 10.1002/ajmg.b.32155
PMID: 24132903
Source
Medline
Keywords
License
Unknown

Abstract

Medications for attention deficit hyperactivity disorder (ADHD) are only partially effective. Ideally, new treatment targets would derive from a known pathophysiology. Such data are not available for ADHD. We combine evidence for new etiologic pathways with bioinformatics data to assess the possibility that existing drugs might be repositioning for treating ADHD. We use this approach to determine if prior data implicating the sodium/hydrogen exchanger 9 gene (SLC9A9) in ADHD implicate sodium/hydrogen exchange (NHE) inhibitors as potential treatments. We assessed the potential for repositioning by assessing the similarity of drug-protein binding profiles between NHE inhibitors and drugs known to treat ADHD using the Drug Repositioning and Adverse Reaction via Chemical-Protein Interactome server. NHE9 shows a high degree of amino acid similarity between NHE inhibitor sensitive NHEs in the region of the NHE inhibitor recognition site defined for NHE1. We found high correlations in drug-protein binding profiles among most ADHD drugs. The drug-protein binding profiles of some NHE inhibitors were highly correlated with ADHD drugs whereas the profiles for a control set of nonsteroidal anti-inflammatory drugs (NSAIDs) were not. Further experimental work should evaluate if NHE inhibitors are suitable for treating ADHD.

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