Can calcium antagonists provide a neuroprotective effect in Parkinson's disease?

摘要

Although major strides forward have been made in the symptomatic treatment of Parkinson's disease (PD), effective neuroprotective therapies have not yet been perfected. The role of calcium in neurotoxicity, and specifically in mediating the process of apoptosis, raises the possibility that calcium antagonists may have a salutary effect on conditions such as PD in which apoptosis may be the ultimate mode of cell death. Several lines of evidence support this notion including the reported effect of calcium antagonists on other human diseases involving apoptosis and animal studies demonstrating the ability of calcium antagonists to protect substantia nigra neurons from the toxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The common calcium antagonists in use for the treatment of cardiovascular diseases have the potential to modify calcium neurotoxicity in PD since they block L-type calcium channels which are predominantly responsible for regulating intracellular calcium in midbrain dopaminergic cells. The widespread use of these agents affords the opportunity to discern their effect on PD through population studies. Preliminary investigations of this type have been performed to date, suggesting that calcium antagonist use may be less common in hypertensive PD patients than in non-PD hypertensive patients. More extensive investigations of this type, and prospective studies of calcium antagonist use in PD will be required to determine if these agents truly have a salutary effect on Parkinsonism.