Abstract

Peripheral decarboxylase inhibitors (PDIs) prevent conversion of levodopa to dopamine in the blood by the enzyme aromatic L-amino acid decarboxylase (AADC). Alterations in enzyme activity may contribute to the required higher dosages of levodopa observed in many patients with Parkinson’s disease. We evaluated the effect of levodopa/PDI use on serum AADC enzyme activity. Serum AADC enzyme activity was evaluated in three independent cohorts of patients with Parkinson’s disease or parkinsonism (n = 301) and compared between patients on levodopa/PDI vs. patients not on this medication. AADC enzyme activity was elevated in 62% of patients on levodopa/PDI treatment, compared to 19% of patients not on levodopa/PDI (median 90 mU/L vs. 50 mU/L, p < 0.001). Patients with elevated AADC activity had longer disease duration and higher doses of levodopa/PDI. These findings may implicate that peripheral AADC induction could underlie a waning effect of levodopa, necessitating dose increases to maintain a sustained therapeutic effect.

Details

Title
Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase
Author
Anouke, van Rumund 1   VIAFID ORCID Logo  ; Pavelka Lukas 2 ; Esselink Rianne A J 1 ; Geurtz Ben P M 3 ; Wevers, Ron A 3   VIAFID ORCID Logo  ; Mollenhauer Brit 4 ; Krüger Rejko 5 ; Bloem, Bastiaan R 1 ; Verbeek, Marcel M 6 

1  Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605); Radboudumc Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands (GRID:grid.5590.9) 
2  University of Luxembourg, Clinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette, Luxembourg (GRID:grid.16008.3f) (ISNI:0000 0001 2295 9843); Centre Hospitalier de Luxembourg, Parkinson’s Research Clinic, Luxembourg, Luxembourg (GRID:grid.418041.8) (ISNI:0000 0004 0578 0421) 
3  Radboud University Medical Center, Department of Laboratory Medicine, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
4  Center of Parkinsonism and Movement Disorders, Paracelsus-Elena-Klinik, Kassel, Germany (GRID:grid.440220.0); University Medical Center, Department of Neurology, Göttingen, Germany (GRID:grid.411984.1) (ISNI:0000 0001 0482 5331) 
5  University of Luxembourg, Clinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine, Esch-sur-Alzette, Luxembourg (GRID:grid.16008.3f) (ISNI:0000 0001 2295 9843); Centre Hospitalier de Luxembourg, Parkinson’s Research Clinic, Luxembourg, Luxembourg (GRID:grid.418041.8) (ISNI:0000 0004 0578 0421); Luxembourg Institute of Health, Transversal Translational Medicine, Strassen, Luxembourg (GRID:grid.451012.3) (ISNI:0000 0004 0621 531X) 
6  Donders Institute for Brain, Cognition and Behaviour, Department of Neurology, Radboud University Medical Center, Nijmegen, The Netherlands (GRID:grid.5590.9) (ISNI:0000000122931605); Radboud University Medical Center, Department of Laboratory Medicine, Nijmegen, The Netherlands (GRID:grid.10417.33) (ISNI:0000 0004 0444 9382) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
23738057
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41531-021-00172-z
ProQuest document ID
2503046206
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.