Altered pharmacokinetics of L-dopa metabolism in rat striatum deprived of dopaminergic innervation.

Rats with unilateral lesions of the substantia nigra were treated with L-dopa 25 mg/kg subcutaneously 30 minutes after treatment with carbidopa 25 mg/kg intraperitoneally. In the ipsilateral striatum, dopamine levels achieved a peak of 1.57 +/- 0.63 micrograms/g (control 0.19 +/- 0.05 micrograms/g) at 20 minutes and did not differ from controls by 90 minutes after L-dopa administration. Dopamine levels peaked in the contralateral striatum at 45 minutes (11.96 +/- 0.14 micrograms/g, where control levels were 7.74 +/- 0.22 micrograms/g) and returned to control values by 180 minutes. These data suggest that in patients with advanced Parkinson's disease, L-dopa administration results in a smaller increase and a shorter duration of elevation in striatal dopamine concentration than in controls. These observations support the hypothesis that the "wearing-off" phenomenon that occurs during the treatment of patients with Parkinson's disease occurs as a consequence of a reduction in the rate of conversion of L-dopa to dopamine and perhaps diminished capacity for the storage of dopamine.