Is continuous dopaminergic delivery still a major goal to be achieved in the treatment of Parkinson's disease?

Dopaminergic drugs represent the cornerstone in the symptomatic management of Parkinson's disease motor manifestations, although their long-term use is associated with the appearance of motor fluctuations and dyskinesias. The correlation between pulsatile plasmatic levels of dopaminergic drugs and motor complications suggested that a central continuous dopaminergic stimulation (CDS) could prevent their development. Therefore, several methods have been implemented to provide more stable plasmatic levels of dopaminergic drugs and obtain a continuous drug delivery (CDD). Nevertheless, CDD does not necessarily mean CDS, since other peripheral pharmacokinetic factors intervene before the striatal dopamine release, along with central pharmacodynamic mechanisms. Here, we provide an overview of the different pharmacological approaches taken over time to reach CDS, with limitations and questions that remain open.