18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease.
Tolcapone is a potent, selective, and reversible inhibitor of cathecol-O-methyl-transferase (COMT). This enzyme plays a crucial role in the extraneural inactivation of catecholamine neurotransmitters. Tolcapone's ability to inhibit central COMT in humans at therapeutic concentrations is not yet clear. The aim was to determine the effect of tolcapone on central COMT activity in Parkinson's disease (PD) using (18)F-dopa positron emission tomography (PET). The study was a randomized two-way crossover study. Twelve PD patients were recruited. On the treatment days patients were given either tolcapone (200 mg) or placebo together with levodopa/carbidopa (100/125 mg) 1 h before the injection of (18)F-dopa. Data were acquired in 25 frames over 94 min for the first PET scan period. At the end of this period the patients were removed from the scanner for 90 min and subsequently repositioned and data acquired in six 10-min time frames over 60 min. Influx constants (Ki) were computed using a graphical approach with a plasma input function. Mean (18)F-dopa putamen Ki's for the first 30-90 min, primarily reflecting central dopa decarboxylase (DDC) activity, were similar in PD patients whether tolcapone was present (0.0078 +/- 0.0031 min(-1)) or absent (0.0078 +/- 0.0030 min(-1)). Mean putamen Ki values calculated 180-240 min after injection of (18)F-dopa, reflecting both central DDC and COMT activity, were unchanged from 30-90' values in the presence of tolcapone (0.0079 +/- 0.0030), implying blockade of central COMT, but were significantly reduced (0.0059 +/- 0.0028) in the absence of this drug. These findings are compatible with clinical doses of tolcapone having a significant blocking effect on peripheral and central COMT but not DDC activity in PD.[1]References
- 18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease. Ceravolo, R., Piccini, P., Bailey, D.L., Jorga, K.M., Bryson, H., Brooks, D.J. Synapse (2002) [Pubmed]
Annotations and hyperlinks in this abstract are from individual authors of WikiGenes or automatically generated by the WikiGenes Data Mining Engine. The abstract is from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.About WikiGenesOpen Access LicencePrivacy PolicyTerms of Useapsburg
