Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009, Article ID 969752, 5 pages

Possible Treatment Concepts for the Levodopa-Related Hyperhomocysteinemia

Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088 Berlin, Germany

Received 26 April 2009; Revised 13 June 2009; Accepted 16 July 2009

Academic Editor: Hari Manev

Copyright © 2009 Thomas Müller. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The saga of harmful levodopa (LD) in the treatment of Parkinson's disease (PD) resulted from outcomes of animal—and cell culture studies and the clinical observation of motor complication related to the short half life of LD. Further aspects of LD long term application, the LD associated homocysteine increase and its emerging consequences on progression, and onset of neuropsychiatric symptoms and of vascular disease are only partially considered. Therapeutic approaches for this LD-mediated neurotoxic homocysteine increase are vitamin supplementation or LD application with an inhibitor of catechol-O-methyltransferase (COMT). However, forcing central dopamine metabolism further down the methylation path by central blocking of COMT and MAO-B may reduce oxidative stress and homocysteine levels. But it may also increase N-methylation of tetrahydroisoquinolines to neurotoxic N-methylated tetrahydroisoquinolines. These compounds were observed in cerebrospinal fluid and plasma of long term LD-treated PD patients. Therefore LD application with peripheral COMT inhibition may be safer.