Levodopa-related cysteinyl–glycine and cysteine reduction with and without catechol-O-methyltransferase inhibition in Parkinson’s disease patients

Oxidative stress is influenced by the thiol homeostasis, which regulates the redox milieu via glutathione. Components of glutathione metabolism are cysteine and cysteinyl–glycine. Both substrates decay following levodopa application or dopamine-related oxidative stress. Objective was to investigate the impact of an acute levodopa application with and without catechol-O-methyltransferase inhibitor on cysteine- and cysteinyl–glycine plasma levels. On two investigation days, 13 patients with Parkinson’s disease took one retarded release 200-mg levodopa/50 mg carbidopa-containing tablet or one 150-mg levodopa/50-mg carbidopa/200-mg entacapone formulation under standardized conditions. Levodopa, 3-O-methyldopa, cysteine and cysteinyl–glycine were measured at baseline, 80 and 140 min following levodopa administration. Cysteine and cysteinyl–glycine similarly decreased, levodopa was nearly equal during both conditions. Entacapone lowered 3-O-methyldopa. Cysteine decay may be due to an elevated glutathione generation, which consumes cysteine. Cysteinyl–glycine decrease results from the alternative glutathione transformation to its oxidized form glutathione dissulfide after free radical scavenging.