Evaluation of new treatment strategies for Parkinson's disease in animal models : the therapeutic efficacy of the dopamine D1 antagonist SKF 83959 and the neuroprotective agent CGP 3466B

摘要

Parkinson's disease is a progressive neurodegenerative disorder, characterized by a loss of dopamine neurons in the substantia nigra pars compacta. The current medical treatments for patients with this disease have two major disadvantages: they induce severe response complications on the longer term and do not inhibit the progression of the neurodegenerative process underlying the disease. Consequently, therapy can be improved by the development of alternative 'symptomatic' treatments that induce less response complications and new 'protective' treatments that are capable of inhibiting the detrimental process of neurodegeneration. The aim of the present study was to increase the insight in the effectiveness of such new pharmaco-therapies, using the MPTP-treated primate and the 6-OHDA-treated rat as models of the disease. Firstly, this study shows that the bilaterally but not the unilaterally MPTP-treated rhesus monkey is a valid model for predicting the clinical efficacy of such new treatments. Secondly, the symptomatic treatment SKF 83959 was found to have clear therapeutic effects and limited side effects that wore off in time in the bilaterally MPTP-treated rhesus monkey, despite the fact that this compound was found to be an antagonist to primate AC-coupled D1 receptors. Finally, the neuroprotective agent CGP 3466B prevented behavioral and morphological deficits in rats with 6-OHDA-induced lesions in the substantia nigra.Taken together, the present study may contribute to improvements in the treatment of Parkinson's disease