Molecular mechanism underlying levodopa-induced dyskinesia

Paolo Calabresi, Massimiliano Di Filippo, Veronica Ghiglieri, Barbara Picconi

Research output: Contribution to journalArticlepeer-review


Althougb levodopa remains the most effective drug for the symptomatic treatment of Parkinson's disease, chronic therapy with this pharmacological compound initiates a complex cascade of cellular and molecular downstream effects resulting in the development of abnormal involuntary movements. The precise mechanisms underlying the development of levodopa induced dyskinesia, however, are far from being completely elucidated. In the present review, we will describe changes in long-term synaptic excitability following dopamine (DA) denervation and long-term levodopa treatment leading to abnormal involuntary movements. In particular, we will address the role of both DA D1 receptors and NMDA glutamate receptors in the induction and maintenance of dyskinesia and abnormal synaptic plasticity. We will also describe the possible interaction between these two receptors in the pathophysiology of dyskinesia taking the advantage of the existing knowledge concerning the mechanisms underlying drug abuse. This latter pathophysiological condition, in fact, seems to share several biochemical transduction pathways with those implicated in levodopa-induced dyskinesia. Finally, we will briefly discuss the possible implication of A2A adenosine receptors in long-term motor complications of levodopa therapy and focus on the interaction between A2A and D2 receptors. Future studies are required to understand how the interaction between these various biochemical steps converge to produce a long-term change in neuronal excitability within the basal ganglia leading to abnormal involuntary movements following levodopa treatment in the DA-denervated state.

Original languageEnglish
JournalMovement Disorders
Issue numberSUPPL. 3
Publication statusPublished - 2008


  • Dyskinesia
  • L-dopa
  • Parkinson's disease
  • Synaptic plasticity

ASJC Scopus subject areas

  • Medicine(all)
  • Clinical Neurology
  • Neurology


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