title: Can sodium/hydrogen exchange inhibitors be repositioned for treating attention deficit hyperactivity disorder? An in silico approach.
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.
authors.affiliation: Department of Psychiatry, SUNY Upstate Medical University, Syracuse, New York; Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, New York.
authors.forename: Stephen V
authors.initials: SV
authors.lastname: Faraone
authors.forename: Yanli
authors.initials: Y
authors.lastname: Zhang-James
mesh_terms: D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D003198:Computer Simulation; D058492:Drug Repositioning; D006801:Humans; D049990:Membrane Transport Modulators / Q000494:pharmacology* / Q000627:therapeutic use*; D011485:Protein Binding / Q000187:drug effects; D017386:Sequence Homology, Amino Acid; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D049990:Membrane Transport Modulators; D017923:Sodium-Hydrogen Exchangers
keywords: ADHD; NHE9; SLC9A9; drug repositioning; genetics; sodium-hydrogen inhibitors; sodium/hydrogen exchange