title: Detection of tolcapone in the cerebrospinal fluid of parkinsonian subjects.
abstract: The cerebral availability of the peripherally and centrally acting catechol-O-methyltransferase (COMT) inhibitor tolcapone is not known in humans. Therefore, we determined the concentration of tolcapone in cerebrospinal fluid (CSF) of 12 parkinsonian subjects 1-4 h after oral application of 200 mg of the drug. The mean concentration was 56.4+/-35.5 nmol/l (mean +/- SD). This concentration was calculated to cause 75.2+/-15% (mean +/- SD) inhibition of COMT in CSF. Thus, tolcapone efficiently inhibits COMT after crossing the blood-brain barrier in humans.
authors.affiliation: Department of Neurology, University of Regensburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Russ
authors.forename: T
authors.initials: T
authors.lastname: Müller
authors.forename: D
authors.initials: D
authors.lastname: Woitalla
authors.forename: A
authors.initials: A
authors.lastname: Rahbar
authors.forename: J
authors.initials: J
authors.lastname: Hahn
authors.forename: W
authors.initials: W
authors.lastname: Kuhn
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D001577:Benzophenones / Q000008:administration & dosage / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D001812:Blood-Brain Barrier; D002394:Catechol O-Methyltransferase / Q000134:cerebrospinal fluid; D065098:Catechol O-Methyltransferase Inhibitors; D002851:Chromatography, High Pressure Liquid; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000134:cerebrospinal fluid*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009596:Nitrophenols; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000188:drug therapy*; D000077867:Tolcapone
chemical_list: D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D009596:Nitrophenols; D000077867:Tolcapone; D002394:Catechol O-Methyltransferase