On-off effects in Parkinson's disease: a controlled investigation of ascorbic acid therapy.
Patients with PD who experience on-off effects have higher erythrocyte catechol-O-methyltransferase (COMT) activities and plasma 3-O-methyldopa concentrations than do patients without these levodopa-related motor fluctuations. We therefore administered ascorbic acid, a weak competitive inhibitor of COMT, to six PD patients with on-off effects. In this double-blind crossover investigation, ascorbic acid produced a modest improvement in functional performance. However, no fundamental change was observed in the pattern of on-off effects, severity of parkinsonism/dyskinesia, or self-assessment ratings. Ascorbic acid therapy reduced plasma concentrations of levodopa and 3-O-methyldopa but did not alter erythrocyte COMT activity. These findings are discussed in the context of the pharmacokinetic and pharmacodynamic factors that contribute to the pathogenesis of levodopa-induced dyskinesias and on-off motor fluctuations.
D000368:Aged; D001205:Ascorbic Acid / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007980:Levodopa / Q000009:adverse effects* / Q000097:blood; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000139:chemically induced / Q000188:drug therapy; D010300:Parkinson Disease / Q000188:drug therapy*
D007980:Levodopa; D001205:Ascorbic Acid