The motor symptoms of Parkinson's disease (PD) are due to the progressive loss 
of dopamine (DA) neurons in substantia nigra pars compacta (SNc). Nothing is 
known to slow the progression of the disease, making the identification of 
potential neuroprotective agents of great clinical importance. Previous studies 
using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have 
shown that antagonism of L-type Ca2+ channels protects SNc DA neurons. However, 
this was not true in a 6-hydroxydopamine (6-OHDA) model. One potential 
explanation for this discrepancy is that protection in the 6-OHDA model requires 
greater antagonism of Cav1.3 L-type Ca2+ channels thought to underlie 
vulnerability and this was not achievable with the low affinity dihydropyridine 
(DHP) antagonist used. To test this hypothesis, the DHP with the highest 
affinity for Cav1.3L-type channels-isradipine-was systemically administered and 
then the DA toxin 6-OHDA injected intrastriatally. Twenty-five days later, 
neuroprotection and plasma concentration of isradipine were determined. This 
analysis revealed that isradipine produced a dose-dependent sparing of DA fibers 
and cell bodies at concentrations achievable in humans, suggesting that 
isradipine is a potentially viable neuroprotective agent for PD.