title: Improving L-dopa therapy: the development of enzyme inhibitors.
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.
authors.affiliation: Institute of Neuroscience, Favaloro Foundation University Hospital, Solis 461, Buenos Aires, Argentina.
authors.forename: Oscar S
authors.initials: OS
authors.lastname: Gershanik
mesh_terms: D000818:Animals; D015259:Dopamine Agents / Q000627:therapeutic use*; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008996:Monoamine Oxidase Inhibitors / Q000627:therapeutic use*; D010300:Parkinson Disease / Q000188:drug therapy*
chemical_list: D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D007980:Levodopa
keywords: catechol-O-methyl transferase inhibitors; dopa-decarboxylase inhibitors; levodopa; monoamineoxidase inhibitors; pharmacokinetics