Effects of monoamine oxidase and catechol-O-methyltransferase inhibition on dopamine turnover: a PET study with 6-[18F]L-DOPA.

ABSTRACT

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.