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Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction.
Synapse. 1997 Dec; 27(4):336-46.S

Abstract

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-[18F]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 (k3R0), increased significantly after entacapone + selegiline administration in all subject populations. The FDOPA uptake rate constant (Ki) 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 (K1D) or the relative dopadecarboxylase activity (k3D). 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.

Authors+Show Affiliations

Department of Neurology, University of Turku, Finland. hanna.ruottinen@utu.fiNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

9372556

Citation

Ruottinen, H M., et al. "Striatal 6-[18F]fluorodopa Accumulation After Combined Inhibition of Peripheral catechol-O-methyltransferase and Monoamine Oxidase Type B: Differing Response in Relation to Presynaptic Dopaminergic Dysfunction." Synapse (New York, N.Y.), vol. 27, no. 4, 1997, pp. 336-46.
Ruottinen HM, Rinne JO, Oikonen VJ, et al. Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction. Synapse. 1997;27(4):336-46.
Ruottinen, H. M., Rinne, J. O., Oikonen, V. J., Bergman, J. R., Haaparanta, M. T., Solin, O. H., Ruotsalainen, U. H., & Rinne, U. K. (1997). Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction. Synapse (New York, N.Y.), 27(4), 336-46.
Ruottinen HM, et al. Striatal 6-[18F]fluorodopa Accumulation After Combined Inhibition of Peripheral catechol-O-methyltransferase and Monoamine Oxidase Type B: Differing Response in Relation to Presynaptic Dopaminergic Dysfunction. Synapse. 1997;27(4):336-46. PubMed PMID: 9372556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Striatal 6-[18F]fluorodopa accumulation after combined inhibition of peripheral catechol-O-methyltransferase and monoamine oxidase type B: differing response in relation to presynaptic dopaminergic dysfunction. AU - Ruottinen,H M, AU - Rinne,J O, AU - Oikonen,V J, AU - Bergman,J R, AU - Haaparanta,M T, AU - Solin,O H, AU - Ruotsalainen,U H, AU - Rinne,U K, PY - 1998/2/12/pubmed PY - 2000/6/20/medline PY - 1998/2/12/entrez SP - 336 EP - 46 JF - Synapse (New York, N.Y.) JO - Synapse VL - 27 IS - 4 N2 - 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-[18F]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 (k3R0), increased significantly after entacapone + selegiline administration in all subject populations. The FDOPA uptake rate constant (Ki) 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 (K1D) or the relative dopadecarboxylase activity (k3D). 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. SN - 0887-4476 UR - https://www.unboundmedicine.com/medline/citation/9372556/Striatal_6_[18F]fluorodopa_accumulation_after_combined_inhibition_of_peripheral_catechol_O_methyltransferase_and_monoamine_oxidase_type_B:_differing_response_in_relation_to_presynaptic_dopaminergic_dysfunction_ L2 - https://doi.org/10.1002/(SICI)1098-2396(199712)27:4<336::AID-SYN7>3.0.CO;2-D DB - PRIME DP - Unbound Medicine ER -