Pathophysiology of L-dopa-induced motor and non-motor complications in Parkinson's disease

Prog Neurobiol. 2015 Sep;132:96-168. doi: 10.1016/j.pneurobio.2015.07.002. Epub 2015 Jul 21.

Abstract

Involuntary movements, or dyskinesia, represent a debilitating complication of levodopa (L-dopa) therapy for Parkinson's disease (PD). L-dopa-induced dyskinesia (LID) are ultimately experienced by the vast majority of patients. In addition, psychiatric conditions often manifested as compulsive behaviours, are emerging as a serious problem in the management of L-dopa therapy. The present review attempts to provide an overview of our current understanding of dyskinesia and other L-dopa-induced dysfunctions, a field that dramatically evolved in the past twenty years. In view of the extensive literature on LID, there appeared a critical need to re-frame the concepts, to highlight the most suitable models, to review the central nervous system (CNS) circuitry that may be involved, and to propose a pathophysiological framework was timely and necessary. An updated review to clarify our understanding of LID and other L-dopa-related side effects was therefore timely and necessary. This review should help in the development of novel therapeutic strategies aimed at preventing the generation of dyskinetic symptoms.

Keywords: Animal models; D1 receptor; Dopamine; Dyskinesia; L-dopa; Parkinson's disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antiparkinson Agents / adverse effects*
  • Central Nervous System / drug effects
  • Central Nervous System / physiopathology*
  • Dyskinesia, Drug-Induced / physiopathology*
  • Humans
  • Levodopa / adverse effects*
  • Parkinson Disease / drug therapy

Substances

  • Antiparkinson Agents
  • Levodopa