MONOAMINE OXIDASE AND CATECHOL- O -METHYLTRANSFERASE INHIBITORS
Identifieur interne : 001C90 ( Main/Exploration ); précédent : 001C89; suivant : 001C91MONOAMINE OXIDASE AND CATECHOL- O -METHYLTRANSFERASE INHIBITORS
Auteurs : Andrew Siderowf ; Roger Kurlan [États-Unis]Source :
- Medical Clinics of North America [ 0025-7125 ] ; 1999.
Abstract
Parkinson's disease (PD) is almost unique among neurodegenerative disorders because of the presence of effective treatment for its cardinal motor symptoms. The observation of Hornykiewicz and Ehringer37 of profound dopamine deficiency in postmortem brain specimens of PD patients followed by the demonstration by Cotzias et al15 of the feasibility of treating PD patients with large oral doses of l-dopa is one of the notable successes of modern neurology. Although dopamine replacement is highly effective in the early stages of PD, it is not without problems for patients with advanced disease. After several years of therapy, many patients develop adverse motor effects, including dyskinesia (involuntary movements) and shortened duration of therapeutic response. In addition, concern has been raised25 that l-dopa may accelerate the underlying neuronal degeneration and thus should be used as sparingly as possible. As a result of these problems, alternatives to l-dopa continue to be developed. One such strategy is to use agents that inhibit the peripheral catabolism of l-dopa or the central breakdown of dopamine, thus making more dopamine available at the synapse. Drugs that block the dopamine-metabolizing enzymes catechol- O-methyltransferase (COMT) and monoamine oxidase (MAO) represent examples of this strategy. This article discusses the rationale for such agents and reviews their pharmacology and indications.
Url:
DOI: 10.1016/S0025-7125(05)70113-9
Affiliations:
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