Peripheral COMT inhibition prevents levodopa associated homocysteine increase.

Abstract	Chronic levodopa (LD)/dopadecarboxylase inhibitor (DDI) increases homocysteine generation as side reaction of O-methylation. Aim was to investigate the impact of the peripheral COMT inhibitor entacapone (EN) on plasma concentrations of homocysteine, LD and 3-O-methyl-dopa (3-OMD). Patients with Parkinson's disease (PD) received on two consecutive days in a standardised fashion one single dose of 200 mg retarded release LD/carbidopa (CD) or of 150 mg LD/CD/EN, since both were shown to have simultaneous pharmacokinetic LD behaviour. Homocysteine increased after retarded release LD/CD application, but not following LD/CD/EN intake. Homocysteine was lower during the LD/CD/EN condition 80 min after baseline when compared with its levels after LD/CD administration. LD levels simultaneously rose on both days. 3-OMD concentrations did not change. Acute LD/CD application caused a rise of homocysteine levels, which was prevented by LD/CD/EN intake. Therefore, peripheral COMT inhibition may have a beneficial effect on putative, controversially debated components of homocysteine-related progression of PD.
Authors	Thomas Müller, Siegfried Muhlack
Journal	Journal of neural transmission (Vienna, Austria : 1996) (J Neural Transm (Vienna)) Vol. 116 Issue 10 Pg. 1253-6 (Oct 2009) ISSN: 1435-1463 [Electronic] Austria
PMID	19657587 (Publication Type: Journal Article)
Chemical References	Antiparkinson Agents Catechol O-Methyltransferase Inhibitors Catechols Delayed-Action Preparations Enzyme Inhibitors Nitriles Homocysteine Tyrosine Levodopa entacapone Dihydroxyphenylalanine Carbidopa 3-methoxytyrosine
Topics	Adult Aged Aged, 80 and over Antiparkinson Agents (administration & dosage, blood, pharmacology) Carbidopa (administration & dosage, pharmacology) Catechol O-Methyltransferase Inhibitors Catechols (pharmacology) Delayed-Action Preparations Dihydroxyphenylalanine (analogs & derivatives, blood) Enzyme Inhibitors (pharmacology) Female Homocysteine (blood) Humans Levodopa (administration & dosage, blood, pharmacology) Male Middle Aged Nitriles (pharmacology) Parkinson Disease (blood, drug therapy) Time Factors Tyrosine (analogs & derivatives)

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