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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3eebeb9442ff4f699abd025afeca8d9b
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spelling	oai:doaj.org-article:3eebeb9442ff4f699abd025afeca8d9b2021-12-02T16:31:18ZPeripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase10.1038/s41531-021-00172-z2373-8057https://doaj.org/article/3eebeb9442ff4f699abd025afeca8d9b2021-03-01T00:00:00Zhttps://doi.org/10.1038/s41531-021-00172-zhttps://doaj.org/toc/2373-8057Abstract 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.Anouke van RumundLukas PavelkaRianne A. J. EsselinkBen P. M. GeurtzRon A. WeversBrit MollenhauerRejko KrügerBastiaan R. BloemMarcel M. VerbeekNature PortfolioarticleNeurology. Diseases of the nervous systemRC346-429ENnpj Parkinson's Disease, Vol 7, Iss 1, Pp 1-5 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurology. Diseases of the nervous system RC346-429
spellingShingle	Neurology. Diseases of the nervous system RC346-429 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
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.
format	article
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
title	Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase
title_short	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_sort	peripheral decarboxylase inhibitors paradoxically induce aromatic l-amino acid decarboxylase
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/3eebeb9442ff4f699abd025afeca8d9b
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Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase

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