Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase
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 di...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-021-00172-z |
| _version_ | 1797641270122774528 |
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| author | Anouke van Rumund Lukas Pavelka Rianne A. J. Esselink Ben P. M. Geurtz Ron A. Wevers Brit Mollenhauer Rejko Krüger Bastiaan R. Bloem Marcel M. Verbeek |
| author_facet | Anouke van Rumund Lukas Pavelka Rianne A. J. Esselink Ben P. M. Geurtz Ron A. Wevers Brit Mollenhauer Rejko Krüger Bastiaan R. Bloem Marcel M. Verbeek |
| author_sort | Anouke van Rumund |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T13:43:08Z |
| format | Article |
| id | doaj.art-3eebeb9442ff4f699abd025afeca8d9b |
| institution | Directory Open Access Journal |
| issn | 2373-8057 |
| language | English |
| last_indexed | 2024-03-11T13:43:08Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj.art-3eebeb9442ff4f699abd025afeca8d9b2023-11-02T11:18:42ZengNature Portfolionpj Parkinson's Disease2373-80572021-03-01711510.1038/s41531-021-00172-zPeripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylaseAnouke van Rumund0Lukas Pavelka1Rianne A. J. Esselink2Ben P. M. Geurtz3Ron A. Wevers4Brit Mollenhauer5Rejko Krüger6Bastiaan R. Bloem7Marcel M. Verbeek8Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and BehaviourClinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine, University of LuxembourgDepartment of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and BehaviourDepartment of Laboratory Medicine, Radboud University Medical CenterDepartment of Laboratory Medicine, Radboud University Medical CenterCenter of Parkinsonism and Movement Disorders, Paracelsus-Elena-KlinikClinical and Experimental Neuroscience, Luxembourg Centre for Systems Biomedicine, University of LuxembourgDepartment of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and BehaviourDepartment of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and BehaviourAbstract 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.https://doi.org/10.1038/s41531-021-00172-z |
| spellingShingle | Anouke van Rumund Lukas Pavelka Rianne A. J. Esselink Ben P. M. Geurtz Ron A. Wevers Brit Mollenhauer Rejko Krüger Bastiaan R. Bloem Marcel M. Verbeek Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase npj Parkinson's Disease |
| title | Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase |
| title_full | Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase |
| title_fullStr | Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase |
| title_full_unstemmed | Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase |
| title_short | Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase |
| title_sort | peripheral decarboxylase inhibitors paradoxically induce aromatic l amino acid decarboxylase |
| url | https://doi.org/10.1038/s41531-021-00172-z |
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