Question

Why is l-dopa effective in treating parkinson's patients, but not dopamine?

Answer 1

Peripherally administered (outside of the central nervous system) dopamine is not effective because it cannot cross the blood brain barrier.4  The reason for its inability to cross the blood brain barrier has to do with at least two influencing factors.  The first is that dopamine is a hydrophilic molecule that has a greater degree of difficulty in crossing cell membranes.  The second is the absence of a transporter for dopamine to get past the blood brain barrier and into the brain.6  Since the increase in dopamine concentrations are needed in the brain and the peripheral administration of dopamine cannot get into the brain, it does not work in the management of symptoms seen in Parkinson's disease.  However, the precursor to dopamine, L-dopa, is able to get into the brain via a sodium-independent transport system called, large neutral amino acid carrier system or L (leucine) system.7  Once L-dopa gets inside the brain it can then be metabolized by dopa decarboxylase or amino acid decarboxylase to form dopamine within the dopaminergic neurons within the substantia nigra.4  Therefore, L-dopa versus peripherally administered dopamine is currently the main medication used in the management of symptoms associated with Parkinson's disease.