Levodopa-induced dyskinesia in Parkinson's disease

Levodopa-induced dyskinesias (LID) are abnormal involuntary movements that develop progressively with repeated dopamine replacement therapy in Parkinson's disease (PD). The pathophysiology of LID comprises many functionally-related abnormalities in neurotransmission which lead to abnormalities in the rate, pattern and synchronisation of neuronal activity within and outside the basal ganglia. In this review, we discuss the significance of the problem of LID, options currently available for avoiding and treating LID, recent advances in understanding the mechanisms responsible for the generation of LID once it has been established. In particular the discussion relates to the mechanisms underlying LID seen while levodopa is exerting its peak anti-parkinsonian actions, as it is this component of LID that is best modelled in animals and, to date, best understood. We do not aim to discuss the mechanisms by which LID is established and evolves, often termed priming, with repeated treatment, though this is an important area that has also witnessed significant advances recently (for recent review, see Blanchet et al., 2004). Finally, we define, where possible, the rationale for multiple novel therapeutic approaches that might help resolve the problem of LID.