Neurodegenerative Disease Parkinson’s Disease

Oral levodopa remains the most effective symptomatic drug for Parkinson’s disease (PD); however, its long-term use is limited by the emergence of motor fluctuations and involuntary movements, particularly in young-onset patients. A growing number of pre-clinical and clinical studies suggest that non-physiological pulsatile stimulation of striatal dopamine (DA) receptors induced by the use of short-acting oral levodopa preparations, which produce swinging levels of synaptic DA, may contribute to the onset of motor fluctuations and dyskinesias. By contrast, more continuous and less pulsatile forms of dopaminergic stimulation delivered by longer-acting oral DA agonists result in a more stable clinical response and delay the development of motor complications, while steady infusions of apomorphine and levodopa can abolish motor fluctuations and dyskinesias.