EFFECTS OF MONOAMINE-OXIDASE AND CATECHOL-O-METHYLTRANSFERASE INHIBITION ON DOPAMINE TURNOVER - A PET STUDY WITH 6-[F-18]L-DOPA

The consequences of monoamine oxidase and catechol-O-methyltransferase inhibition on the effective turnover of dopamine were investigated us ing 6-[F-18]L-3-4-dihydroxyphenylalanine (6-[F-18]L-DOPA) and positron emission tomography. The effective dopamine turnover was expressed as the ratio between the rate of reversibility of 6-[F-18]L-DOPA trappin g (k(loss)) and the rate of uptake of 6-[F-18]L-DOPA (K-i) in the stri atum of normal cynomolgus monkeys. The monkeys received 6-[F-18]L-DOPA scans, untreated or after pretreatment with either the peripheral cat echol-O-methyltransferase inhibitor nitecapone; the peripheral and cen tral catechol-O-methyl-transferase inhibitor tolcapone; the monoamine oxidase inhibitors deprenyl or pargyline; a combination of tolcapone a nd the monoamine oxidase inhibitors. Tolcapone alone or combined with the monoamine oxidase inhibitors produced a significant decrease in th e dopamine turnover (55 to 65%). Neither nitecapone nor monoamine oxid ase inhibition alone produced significant changes. These results may h ave implications for the use of central catechol-O-methyltransferase i nhibitors added to routine levodopa therapy in parkinsonian patients. (C) 1997 Elsevier Science B.V.