From the MPTP-treated primate to the treatment of motor complications in Parkinson's disease

The MPTP-treated primate has proved to be a highly predictive model of the effects of dopaminergic drugs in the symptomatic treatment of Parkinson's disease (PD) and for the avoidance of motor complications. Using MPTP-treated primates, new dopaminergic therapies have been devised alongside novel treatment strategies and novel routes of administration while providing knowledge on how to use dopaminergic drugs in a manner that avoids the onset of motor complications. The use of MPTP-treated primates led to the concept of continuous dopaminergic stimulation (CDS) and the early introduction of dopamine receptor agonists as monotherapy for PD for the prevention of dyskinesia. However, CDS does not explain the differences in dyskinesia induction that exist between L-dopa and dopamine receptor agonists, and a more rationale approach to therapy involves continuous drug delivery (CDD). CDD has been explored in the MPTP-treated primate and this review focuses on some of the evidence showing that the delivery of dopaminergic drugs in PD is key to the avoidance of dyskinesia while maintaining therapeutic efficacy. Other types of motor complication, such as "wearing off" and "on-off" remain to be explored in MPTP-treated primates and the model has yet to be used to examine non-motor components of PD. Despite having been employed for almost 25 years, the MPTP-treated primate has many potential uses in the future that will further improve the treatment of PD. (C) 2009 Elsevier Ltd. All rights reserved.