Egyptian Journal of Basic and Clinical Pharmacology

Egyptian Journal of Basic and Clinical Pharmacology
Vol. 2 (2012), Issue 1, pp. 13-25 
doi:10.11131/2012/101332

Role of pramipexole in delaying L-dopa induced dyskinesia and enhancing the response to L-dopa in 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine-parkinsonian mice

L-dopa remains the most effective treatment for Parkinson‟s disease (PD). However, its effectiveness declines on continuous use, leads to motor complications, and does not modify the progression of the neurodegenerative process. Medical therapy that provides the benefits of l-dopa without motor complications and enhances cell proliferation would be a major advance in the treatment of Parkinson‟s disease (PD). The aim of the current study was to evaluate the role of pramipexole in delaying l-dopa induced dyskinesia and providing neuroprotective effect for the substantia nigra neurons. Additionally, the study was extended to evaluate the impact of this neuroprotective effect in enhancing the response to l-dopa in the 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) model of PD in mice. Mice were allocated to five groups as follows: saline group, MPTP group, l-dopa group, pramipexole group and l-dopa + pramipexole group. Co-administration of pramipexole with l-dopa delayed the priming of l-dopa-induced dyskinesia, improved the motor performance of MPTP-parkinsonian mice throughout the entire period of the experiment and promoting cell proliferation. Therefore, pramipexole seems to be a useful adjunct to l-dopa in the current model of experimental parkinsonism, not only to gain more therapeutic effect and to delay the priming of l-dopa induced dyskinesia but also to reduce dopaminergic neuron loss and promote cell proliferation.