Current strategies in the drug treatment of advanced Parkinson's disease — new modes of dopamine substitution

Abstract

Oral levodopa treatment remains the most efficacious treatment of Parkinson's disease, but the majority of patients treated with a levodopa monotherapy for more than 5 years will develop fluctuations and/or dyskinesias. Important pathophysiological mechanisms are peripheral factors resulting in fluctuating levodopa blood concentrations and central pharmacodynamic changes, possibly due to chronic pulsatile stimulation of dopamine receptors. Continuous dopaminergic stimulation is able to smooth out a fluctuating response to oral levodopa and reduce 'off period' dystonia and the intensity of 'peak dose' dyskinesias. New drug delivery techniques include 'slow release' levodopa preparations and subcutaneous infusions of apomorphine. Future methods of transcutaneous or intramuscular application of dopamine agonists are under development. These methods may help to improve the results of long-term levodopa treatment of parkinsonian patients.