title: New pharmacological avenues for the treatment of L-DOPA-induced dyskinesias in Parkinson's disease: targeting glutamate and adenosine receptors.
abstract: BACKGROUND
  Parkinson's disease (PD) therapy is still centered on the use of L-3,4-dihydroxyphenylalanine (L-DOPA), which is hampered by numerous side effects, including abnormal involuntary movements known as L-DOPA-induced dyskinesias (LIDs). LIDs are the result of pre- and postsynaptic changes at the corticostriatal level, induced by chronic and pulsatile stimulation of striatal dopaminergic receptors. These changes impact on synaptic plasticity and involve also selected, nondopaminergic receptors expressed by striatal projection neurons.
  
  
  METHODS
  Among nondopaminergic receptors, glutamate receptors - NMDA and mGluR5 subtypes in particular - and adenosine A(2A) receptors are those most likely involved in LIDs. The aim of the present review is to summarize results of studies undertaken with specific antagonists of these receptors, first conducted in animal models of LIDs, which in selected cases have been translated into clinical trials.
  
  
  CONCLUSIONS
  Selected antagonists of glutamate and adenosine receptors have been proposed as anti-dyskinetic agents. Promising results have been obtained in preclinical investigations and in initial clinical trials, but long-term safety, tolerability and efficacy studies in patients are still required. The current development of novel antagonists, including tools able to act on receptor mosaics, may provide innovative tools for LIDs management in the next future.
authors.affiliation: IRCCS National Neurological Institute C. Mondino, Interdepartmental Research Center for Parkinson's Disease, Via Mondino 2, 27100 Pavia, Italy. fabio.blandini@mondino.it
authors.forename: Fabio
authors.initials: F
authors.lastname: Blandini
authors.forename: Marie-Therese
authors.initials: MT
authors.lastname: Armentero
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D020820:Dyskinesias / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use*; D017470:Receptors, Glutamate / Q000378:metabolism*; D018047:Receptors, Purinergic P1 / Q000378:metabolism*
chemical_list: D000978:Antiparkinson Agents; D018691:Excitatory Amino Acid Antagonists; D058915:Purinergic P1 Receptor Antagonists; D017470:Receptors, Glutamate; D018047:Receptors, Purinergic P1; D007980:Levodopa