title: Novel NMDA receptor modulators: an update.
abstract: BACKGROUND
  The NMDA receptor is a ligand-gated ion channel that plays a critical role in higher level brain processes and has been implicated in a range of neurological and psychiatric conditions. Although initial studies for the use of NMDA receptor antagonists in neuroprotection were unsuccessful, more recently, NMDA receptor antagonists have shown clinical promise in other indications such as Alzheimer's disease, Parkinson's disease, pain and depression. Based on the clinical observations and more recent insights into receptor pharmacology, new modulatory approaches are beginning to emerge, with potential therapeutic benefit.
  
  
  METHODS
  The article covers the known pharmacology and important features regarding NMDA receptors and their function. A discussion of pre-clinical and clinical relevance is included, as well. The subsequent patent literature review highlights the current state of the art targeting the receptor since the last review in 2010.
  
  
  CONCLUSIONS
  The complex nature of the NMDA receptor structure and function is becoming better understood. As knowledge about this receptor increases, it opens up new opportunities for targeting the receptor for many therapeutic indications. New strategies and advances in older technologies will need to be further developed before clinical success can be achieved. First-in-class potentiators and subunit-selective agents form the basis for most new strategies, complemented by efforts to limit off-target liability and fine-tune on-target properties.
authors.affiliation: Emory University, Department of Chemistry, Atlanta, GA 30322, USA.
authors.forename: Rose M
authors.initials: RM
authors.lastname: Santangelo
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Acker
authors.forename: Sommer S
authors.initials: SS
authors.lastname: Zimmerman
authors.forename: Brooke M
authors.initials: BM
authors.lastname: Katzman
authors.forename: Katie L
authors.initials: KL
authors.lastname: Strong
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Traynelis
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Liotta
mesh_terms: D000818:Animals; D015195:Drug Design; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010330:Patents as Topic; D011487:Protein Conformation; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate