title: Glutamate-based anxiolytic ligands in clinical trials.
abstract: BACKGROUND
  With regard to anxiety, the role of the balance between glutamatergic and GABAergic systems was pursued for many years. The majority of drugs used presently as effective anxiolytics enhance the GABAergic system activity, thus increasing inhibition within the central nervous system (CNS). On the other hand, decreasing the activity of glutamatergic neurotransmission may attenuate excitation in the CNS, thus resulting in anxiolysis.
  
  
  METHODS
  The present review focuses on clinical data of well-known and recently discovered glutamatergic and, to a lesser extent, GABAergic agents, which reached at least the Phase II criteria.
  
  
  CONCLUSIONS
  A variety of glutamatergic agents active at both N-acetylo-D-asparaginian and metabotropic glutamate (mGlu) receptors have been tested in humans to examine their potential anxiolytic activity. Many compounds acting on the glutamatergic system and approved for the treatment of other disorders than anxiety were shown to exert anxiolytic effects in clinical trials. Those are mainly voltage-dependent ion channel ligands as well as d-cycloserin and memantine. Also, ligands active at mGlu receptors, such as fenobam and LY354740, exhibited activity in controlled clinical trials. However, relatively few trials are found on the agents that are focused on GABAergic neurotransmission. Therefore, it seems that glutamatergic system may become a novel target for modern and effective anxiolytics.
authors.affiliation: Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Poland.
authors.forename: Joanna M
authors.initials: JM
authors.lastname: Wierońska
authors.forename: Andrzej
authors.initials: A
authors.lastname: Pilc
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018683:Excitatory Amino Acid Agents / Q000627:therapeutic use*; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008024:Ligands; D013569:Synapses / Q000502:physiology
chemical_list: D014151:Anti-Anxiety Agents; D018683:Excitatory Amino Acid Agents; D007473:Ion Channels; D008024:Ligands; D018698:Glutamic Acid