Current research into
Parkinson's disease (PD) is directed at developing novel agents and strategies for improved symptomatic management. The aim of this research is to provide effective and maintained symptom control throughout the course of the disease without loss of efficacy and without priming the basal ganglia for the onset of
dyskinesia. To achieve these objectives, it is important to have relevant animal models of PD in which new pharmacological agents and treatment strategies can be assessed prior to clinical assessment. At present, the most effective experimental model of PD is the methyl phenyl
tetrahydropyridine (
MPTP)-treated primate. Primates treated with
MPTP develop motor disturbances resembling those seen in idiopathic PD, including
bradykinesia, rigidity and postural abnormalities. In addition,
MPTP-treated primates are responsive to all commonly used
antiparkinsonian agents and display treatment-associated motor complications such as
dyskinesia, wearing-off and on-off, which occur during the long-term treatment of the illness. This review examines how studies conducted in
MPTP-treated primates have contributed to the development of dopaminergic
therapies. There is now accumulating evidence that the pulsatile manner in which short-acting agents stimulate striatal
dopamine receptors is a key contributing factor to the priming of the basal ganglia for
dyskinesia induction. It has been suggested that providing more continuous stimulation of
dopamine receptors will avoid the development of motor complications, particularly
dyskinesia. So far, the actions of all commonly used antiparkinsonian drugs assessed in
MPTP-treated primates have proved to be highly predictive of
drug action in PD. These primate studies have demonstrated that long-acting
dopamine agonists and
levodopa given in combination with a
catechol-O-methyl
transferase (COMT) inhibitor (to increase its relatively short half-life), induce significantly less
dyskinesia than occurs with standard
levodopa therapy.