Half a century of L-DOPA.

L-DOPA is a di-hydroxy-phenyl, catecholamine precursor, amino acid, initially considered as an inert compound and now the key stone for the treatment of Parkinson's disease (PD) and some hereditary dystonias. L-DOPA, when administered to mammals, is rapidly metabolized to dopamine and 3-OM-DOPA, and its half-life in plasma is roughly 2 hours which has been considered the explanation for some of the L-DOPA related complications in PD. There have been, therefore, sophisticated methods of improving its pharmacokinetics by the association of decarboxylase and COMT inhibitors, slow release preparations and continuous infusions. In addition to its symptomatic effects, the impact of L-DOPA on the natural course of the disease is intriguing. By alleviating motor deficits, L-DOPA may improve health quality and life span in patients with PD, but there are neurotoxic and neurotrophic effects of L-DOPA which may produce long term effects on disease progression. These effects are dependent of the dose, the status of the metabolic pathways involved in catecholamine metabolism, the balance of free radicals and their scavengers and the function of glia. Finally, there is new data suggesting that L-DOPA may be not only a catecholamine precursor but also a neurotransmitter by itself of yet unknown function.