Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients.
Homocysteine (Hcy) is a risk factor for vascular diseases, cognitive impairment, and dementia. Elevated plasma concentrations of Hcy have been found recently in Parkinson's disease (PD) patients treated with levodopa, suggesting that levodopa is a cause of hyperhomocysteinemia (HHcy). The mechanism underlying HHcy in PD is the O-methylation of levodopa catalyzed by catechol-O-methyltransferase (COMT) that produces S-adenosylhomocysteine, which is hydrolyzed rapidly to Hcy. COMT inhibitors (COMT-I) are used currently in the treatment of PD; however, no study has assessed the effects of COMT-I administration on Hcy concentrations in PD patients. We compared plasma levels of Hcy, B12, and folate in 26 PD patients treated with levodopa, 20 PD patients treated with levodopa + COMT-I, and 32 controls. No significant differences were found in vitamin B12 levels, whereas folate concentrations were significantly lower in the levodopa-treated group. Plasma Hcy was increased significantly in the two groups of PD patients and was significantly lower in the group treated with levodopa + COMT-I. Statistical analysis showed that the difference in mean Hcy levels observed among PD patients was related to the addition of COMT-I, rather than to folate concentrations. We conclude that levodopa treatment increases plasma Hcy and the addition of COMT-I effectively reduces HHcy.
Lamberti
Paolo
P
Department of Neurological Sciences, University of Bari, Bari, Italy. lamberti@neurol.uniba.it
Zoccolella
Stefano
S
Iliceto
Giovanni
G
Armenise
Elio
E
Fraddosio
Angela
A
de Mari
Michele
M
Livrea
Paolo
P
D000368:Aged; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016022:Case-Control Studies; D002396:Catechols / Q000494:pharmacology* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004359:Drug Therapy, Combination; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009570:Nitriles; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy; D014805:Vitamin B 12 / Q000097:blood
D000978:Antiparkinson Agents; D002396:Catechols; D009570:Nitriles; D006710:Homocysteine; D007980:Levodopa; C071192:entacapone; D005492:Folic Acid; D014805:Vitamin B 12