Improving l-dopa therapy: The development of enzyme inhibitors

• Published in: Movement disorders 2015-01, Vol.30 (1), p.103-113
• Main Author: Gershanik, Oscar S.
• Format: Article
• Language: English
• Subjects: Animals; catechol-O-methyl transferase inhibitors; dopa-decarboxylase inhibitors; Dopamine Agents - therapeutic use; Humans; levodopa; Levodopa - therapeutic use; Monoamine Oxidase Inhibitors - therapeutic use; monoamineoxidase inhibitors; Movement disorders; Parkinson Disease - drug therapy; pharmacokinetics
• ISSN: 0885-3185; 1531-8257
• DOI: 10.1002/mds.26050

ABSTRACT 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. © 2014 International Parkinson and Movement Disorder Society