Levodopa, motor fluctuations and dyskinesia in Parkinson's disease

Parkinson's disease (PD) is one of the most frequent, chronic, progressive degenerative disorders of the CNS, characterised by altered neurotransmission of dopamine in the basal ganglia. This may result in disturbances of movement, mobility and posture symptoms, all of which cause severe disability in PD patients. There is no cure for PD. Current treatment approaches aim at symptomatic improvement with a balance of the altered neurotransmission, particularly in striatal dopaminergic neurons. Levodopa, the metabolic precursor of active dopamine, is the most effective compound in the drug treatment of PD. However, chronic exposure to levodopa and related dopaminergic agents supports an onset of movement behaviour fluctuations and dyskinesia in the long term. Dyskinesia is unwanted, sometimes excessive and causes abnormal facial, body and limb movements that appear in many PD patients who are often dependent on the overall dosage of dopaminergic substitution. This complication of anti-Parkinsonian drug therapy supports disability and reduces quality of life in PD patients and their caregivers. This review focuses on the major clinical features and knowledge on the aetiology of these treatment-associated, long-term side effects of dopmaminergic drug treatment in PD. It also gives an overview of existing and potential future treatment-strategies for the management of these troublesome treatment complications that affect motor behaviour in PD patients.