ABSTRACT
A revolution in the medical treatment of Parkinson’s disease (PD) occurred with the recognition that levodopa (3,4 dihydroxy-L-phenylalanine, Figure 56.1), the direct biochemical precursor to dopamine (DA), replenishes neuronal dopamine stores and improves many of the motor features of PD. Since its introduction over three decades ago, levodopa remains the single most effective drug for alleviating the motor symptoms of PD and is the only drug that improves life span in this progressive disorder.1-7
Levodopa, unlike dopamine (DA), crosses the bloodbrain barrier via large, neutral amino acid transporters (Figure 56.2). Once inside the neuron, levodopa undergoes
rapid decarboxylation by aromatic amino acid decarboxylase to produce DA. Newly synthesized DA is then stored in synaptic vesicles for subsequent release. Since levodopa bypasses the rate-limiting enzyme, tyrosine hydroxylase, administration of this precursor accelerates DA synthesis through mass action, replenishing depleted central DA stores. Replacement of declining concentrations of synap-
tic DA released from nigrostriatal neurons provides the rationale for the therapeutic benefit of levodopa.
