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.
MeSH terms
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Administration, Oral
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Adult
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Aged
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Aged, 80 and over
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Antiparkinson Agents / administration & dosage
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Antiparkinson Agents / adverse effects
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Antiparkinson Agents / cerebrospinal fluid*
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Benzophenones / administration & dosage
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Benzophenones / adverse effects
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Benzophenones / cerebrospinal fluid*
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Blood-Brain Barrier
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Catechol O-Methyltransferase / cerebrospinal fluid
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Catechol O-Methyltransferase Inhibitors
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Chromatography, High Pressure Liquid
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Enzyme Inhibitors / administration & dosage
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Enzyme Inhibitors / adverse effects
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Enzyme Inhibitors / cerebrospinal fluid*
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Female
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Humans
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Male
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Middle Aged
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Nitrophenols
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Parkinson Disease / cerebrospinal fluid*
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Parkinson Disease / drug therapy*
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Tolcapone
Substances
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Antiparkinson Agents
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Benzophenones
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Catechol O-Methyltransferase Inhibitors
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Enzyme Inhibitors
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Nitrophenols
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Tolcapone
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Catechol O-Methyltransferase