Zhigao Huang, MD, PhD, Clinical Fellow,
Ajit Kumar, DM, Clinical Fellow,
Joseph Tsui, MD, FRCPC, Professor, Department of Medicine, University of British Columbia, Vancouver, BC.
Long-term treatment with dopaminomimetic drugs is often complicated by the occurrence of motor complications in Parkinson's Disease (PD) patients. This is especially true with levodopa, which remains to date the mainstay of treatment of PD. These motor complications consist of fluctuations and dyskinesias. Fluctuations refer to predictable or unpredictable changes of motor response that occur in relation to levodopa administration. Dyskinesias refer to abnormal excessive movements. Motor fluctuations can affect up to 50% of PD patients after five years of levodopa treatment.1 The main categories of fluctuations are 'wearing-off' and 'on-off.' Clinically, 'wearing-off' is characterized by a shortened duration of motor response and a rapidly waning effect in response to each oral dose of levodopa. 'On-off' refers to random fluctuations in motor response seemingly unrelated to levodopa administration.2
In early PD, the motor response to levodopa administration lasts longer than would be inferred from the plasma half-life of levodopa. Presumably, this phenomenon is related to surviving nigrostriatal neurons being able to store dopamine (DA) synthesized from exogenous levodopa, thus serving a buffer-like function.