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: | , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/3eebeb9442ff4f699abd025afeca8d9b |
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| Sumario: | 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. |
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