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Mov Disord. 2015 Jan;30(1):103-13. doi: 10.1002/mds.26050. Epub 2014 Oct 21.

Improving L-dopa therapy: the development of enzyme inhibitors.

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Institute of Neuroscience, Favaloro Foundation University Hospital, Solis 461, Buenos Aires, Argentina.


The introduction of levodopa produced a monumental change in the treatment of Parkinson's disease (PD). Limitations in its bioavailability and tolerability led to the search for drugs that could improve its pharmacokinetics and safety profile. Dopa-decarboxylase inhibitors were the first such drugs that were developed, and their use in combination with L-dopa has become standard practice. Increasing knowledge on the metabolism of L-dopa allowed the identification of additional targets for intervention in an attempt to improve the symptomatic efficacy of L-dopa. Monoamineoxidase inhibitors, enhancing the central bioavailability of dopamine by blocking its metabolism, were the next step, and despite controversies regarding their efficacy, they have remained as valuable adjuncts to l-dopa in the treatment of PD. More recently, the introduction of potent, selective catechol-O-methyl transferase inhibitors have found their place in the therapeutic armamentarium of PD and are prescribed in combination with l-dopa to prolong the duration of its action.


catechol-O-methyl transferase inhibitors; dopa-decarboxylase inhibitors; levodopa; monoamineoxidase inhibitors; pharmacokinetics

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