Abstract
The accumulation and metabolism of l-Dopa has been determined in isolated, perfused rat brains in the presence and absence of peripheral DOPA decarboxylase inhibition. As the brain is perfused with increased concentrations of l-Dopa, the tissue DOPA and dopamine levels do not rise in a continuous fashion but rather progress through a series of plateaus and regressions. This phenomenon is not unique to isolated brains but occurs in vivo as well. The inhibition of peripheral DOPA decarboxylase was found to cause a drastic reduction in dopamine accumulation, particularly at low DOPA perfusion levels. Thus, while the presence of DOPA decarboxylase on the peripheral side of the blood-brain barrier is confirmed, the function of an enzymatic blood-brain barrier has not been demonstrated. The decline in brain dopamine levels at critical l-DOPA circulating concentrations may pertain to reverses in the therapeutic effectiveness of l-DOPA observed in some Parkinson patients.
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