Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients

Background: Elevated plasma total homocysteine (tHcy) appeared in levodopa/dopadecarcoxylase inhibitor (DDI) treated patients with Parkinson's disease (PD). One therapeutic approach for tHcy reduction is vitamine supplementation, since folic acid and cobalamine catalyse and enhance metabolism of tHcy to methionine. A further therapeutic alternative is inhibition of catechol-O-methyltransfrase (COMT) on a regular basis, when levodopa/DDI treatment is performed. Methods: We measured the concentrations of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), tHcy, levodopa and 3-O-methyldopa in plasma of 13 levodopa treated PD patients before first drug intake at 0600 hours. Blood samples were taken before and after 2 days of additional application of the centrally acting catechol-O-methyltransferase inhibitor tolcapone 100 mg t.i.d. Results: Plasma levels of SAH [day 1: 48.32 +/- 22.52, 23.92-98.25 (mean +/- SD, range; mu mol/l); day 3: 37.72 +/- 15.84, 23.4-61.89; p=0.01] and tHcy (day 1: 13.88 +/- 5.62, 7.63-24.81; day 3: 11.38 +/- 4.44, 5.98-20.45; p=0.04) significantly reduced. Plasma levels of levodopa did not significantly (p=0.17) increase, whereas 3-OMD concentrations significantly (p=0.0002) reduced after additional tolcapone intake. There was no significant change of SAM plasma levels (p=0.22). Conclusion: Our prospective trial shows, that COMT inhibition with tolcapone lowers tHcy synthesis. Tolcapone may also possess beside its proven, occasional, hepatotoxic potency also beneficial effects via decrease of SAH and tHcy. This may hypothetically reduce homocysteine mediated progress of neuronal degeneration and the risk for onset of dementia, vascular disease and polyneuropathy in levodopa treated PD patients in the long term.