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Striatal 6‐[ 18 F]fluorodopa accumulation after combined inhibition of peripheral catechol‐ O ‐methyltransferase and monoamine oxidase type B: Differing response in relation to presynaptic dopaminergic dysfunction
Author(s) -
Ruottinen Hanna M.,
Rinne Juha O.,
Oikonen Vesa J.,
Bergman Jörgen R.,
Haaparanta Merja T.,
Solin Olof H.,
Ruotsalainen Ulla H.,
Rinne Urpo K.
Publication year - 1997
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(199712)27:4<336::aid-syn7>3.0.co;2-d
Subject(s) - selegiline , entacapone , monoamine oxidase b , pharmacology , levodopa , chemistry , parkinson's disease , dopaminergic , catechol o methyl transferase , monoamine oxidase , dopamine , medicine , endocrinology , biochemistry , enzyme , allele , disease , gene
The aim was to investigate the effects of inhibition of monoamine oxidase type B (MAO‐B) with selegiline alone and the combined inhibition of peripheral catechol‐ O ‐methyltransferase (COMT) with entacapone and MAO‐B with selegiline on striatal 6‐[ 18 F]fluorodopa (FDOPA) accumulation, and whether the effect of entacapone + selegiline on FDOPA uptake differed depending on the severity of the presynaptic dopaminergic dysfunction. Thus, eight healthy controls, eight de novo patients with Parkinson's disease (PD), and 18 levodopa‐treated PD patients were investigated with positron emission tomography (PET). Half of the subjects in each population belonged to the selegiline group and half to the entacapone + selegiline group. Both groups were studied twice with PET using FDOPA. After the first (baseline) FDOPA PET investigation, both groups were on 2 weeks of selegiline treatment, 10 mg daily. Thereafter, the second FDOPA PET was performed for all subjects with a premedication administered 60 min before the PET imaging; one group received 10 mg of selegiline, and the other group received a single 400 mg dose of entacapone coadministered with 10 mg of selegiline. Selegiline treatment alone had no significant influence on striatal FDOPA metabolism. The FDOPA accumulation, expressed as striatal‐to‐occipital ratios and modified decarboxylation coefficients (k 3 R 0 ), increased significantly after entacapone + selegiline administration in all subject populations. The FDOPA uptake rate constant (K i ) remained virtually unchanged in controls and in de novo patients but decreased significantly in levodopa‐treated PD patients after entacapone + selegiline intake. Entacapone + selegiline administration did not influence significantly the unidirectional blood‐to‐brain clearance for FDOPA (K 1 D ) or the relative dopadecarboxylase activity (k 3 D ). The changes in the studied parameters after entacapone + selegiline administration probably reflect the effects of entacapone, since entacapone alone has caused similar changes in previous PET studies. Response in FDOPA accumulation to entacapone + selegiline was higher in controls and de novo patients compared with levodopa‐treated PD patients. The milder response in levodopa‐treated patients might reflect the reduced ability of the degenerated dopaminergic neurons to utilize the prolonged FDOPA availability, produced by entacapone. Synapse 27:336–346, 1997. © 1997 Wiley‐Liss, Inc.