Effects of monoamine oxidase and catechol-O-methyltransferase inhibition on dopamine turnover: a PET study with 6-[18F]L-DOPA.
The consequences of monoamine oxidase and catechol-O-methyltransferase inhibition on the effective turnover of dopamine were investigated using 6-[18F]L-3-4-dihydroxyphenylalanine (6-[18F]L-DOPA) and positron emission tomography. The effective dopamine turnover was expressed as the ratio between the rate of reversibility of 6-[18F]L-DOPA trapping (k[loss]) and the rate of uptake of 6-[81F]L-DOPA (Ki) in the striatum of normal cynomolgus monkeys. The monkeys received 6-[18F]L-DOPA scans, untreated or after pretreatment with either the peripheral catechol-O-methyltransferase inhibitor nitecapone; the peripheral and central catechol-O-methyltransferase inhibitor tolcapone; the monoamine oxidase inhibitors deprenyl or pargyline; a combination of tolcapone and the monoamine oxidase inhibitors. Tolcapone alone or combined with the monoamine oxidase inhibitors produced a significant decrease in the dopamine turnover (55 to 65%). Neither nitecapone nor monoamine oxidase inhibition alone produced significant changes. These results may have implications for the use of central catechol-O-methyltransferase inhibitors added to routine levodopa therapy in parkinsonian patients.
Doudet
D J
DJ
Department of Medicine, University of British Columbia, Vancouver, Canada. ddoudet@interchange.ubc.ca
Chan
G L
GL
Holden
J E
JE
Pate
B D
BD
Morrison
K S
KS
Calne
D B
DB
Ruth
T J
TJ
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism*; D001577:Benzophenones / Q000494:pharmacology*; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005462:Fluorine Radioisotopes; D007980:Levodopa / Q000378:metabolism*; D008252:Macaca fascicularis / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009596:Nitrophenols; D010422:Pentanones / Q000494:pharmacology*; D010865:Pilot Projects; D000077867:Tolcapone; D014055:Tomography, Emission-Computed / Q000379:methods; D014793:Visual Cortex / Q000187:drug effects
D000978:Antiparkinson Agents; D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D002396:Catechols; D004791:Enzyme Inhibitors; D005462:Fluorine Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D009596:Nitrophenols; D010422:Pentanones; D007980:Levodopa; C057364:nitecapone; D000077867:Tolcapone; D004298:Dopamine