摘要
Dopamine (DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson′s disease (PD) and in PD patient with levodopa (L DOPA) induced motor fluctuations,but also in early treatment of the disease. This shift has been largely due to the demonstrated L DOPA sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies. In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury. Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical scavenging enzymes,and enhancing neurotrophic activity. The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase 3 in cytoplasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer′s disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists. Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on going clinical trials are promising. Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as 18 F L DOPA PET and 123 I β CIT SPECT. The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.
Dopamine (DA) agonists are playing increasingly important role in the treatment of not only advanced Parkinson′s disease (PD) and in PD patient with levodopa (L DOPA) induced motor fluctuations,but also in early treatment of the disease. This shift has been largely due to the demonstrated L DOPA sparing effect of DA agonists and their putative neuroprotective effect,based largely on experimental in vitro and in vivo studies. In this article we review the evidence of neuroprotection by DA agonists pramipexole,ropinirole,pergolide,bromocriptine and apomorphine in cell cultures and animal models of nigral injury. Most of the studies suggest that DA agonists exert their neuroprotection via directly scavenging free radicals or increasing the activities of radical scavenging enzymes,and enhancing neurotrophic activity. The finding that pramipexole can normalize mitochondrial membrane potential and inhibit activity of caspase 3 in cytoplasmic hybrid cells made from mitochondrial DNA of nonfamilial Alzheimer′s disease patients,however,suggests even a broader implication for the neuroprotective role of DA agonists. Although the clinical evidence for neuroprotection by DA agonists is still limited,the preliminary results from several on going clinical trials are promising. Several longitudinal studies are currently in progress designed to demonstrate a delay or slowing of progresion of PD using various surrogate markers of neuronal degeneration such as 18 F L DOPA PET and 123 I β CIT SPECT. The results of these experimental and clinical studies will improve our understanding of the action of DA agonists and provide critical information needed for planning future therapeutic strategies in PD and related neurodegenerative disorders.
