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Parkinsonism Relat Disord. 2003 Jan;9(3):131-7.

The contribution of the MPTP-treated primate model to the development of new treatment strategies for Parkinson's disease.

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1
Neurodegenerative Disease Research Centre, Hodgkin Building, GKT School of Biomedical Sciences, King's College, SE1 1UL, London, UK. div.pharm@kcl.ac.uk

Abstract

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.

PMID:
12573867
[Indexed for MEDLINE]
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