Peripheral COMT inhibition prevents levodopa associated homocysteine increase.
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.
Müller
Thomas
T
Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Gartenstr. 1, 13088, Berlin, Germany. th.mueller@alexius.de
Muhlack
Siegfried
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D002230:Carbidopa / Q000008:administration & dosage / Q000494:pharmacology; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D003692:Delayed-Action Preparations; D004295:Dihydroxyphenylalanine / Q000031:analogs & derivatives / Q000097:blood; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000494:pharmacology*; D010300:Parkinson Disease / Q000097:blood / Q000188:drug therapy; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives
D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D003692:Delayed-Action Preparations; D004791:Enzyme Inhibitors; D009570:Nitriles; D006710:Homocysteine; D014443:Tyrosine; D007980:Levodopa; C071192:entacapone; D004295:Dihydroxyphenylalanine; D002230:Carbidopa; C008404:3-methoxytyrosine