Peripheral decarboxylase inhibitors paradoxically induce aromatic L-amino acid decarboxylase.

  • Transversal Translational Medicine
March 19, 2021 By:
  • van Rumund A
  • Pavelka L
  • Esselink RAJ
  • Geurtz BPM
  • Wevers RA
  • Mollenhauer B
  • Kruger R
  • Bloem BR
  • Verbeek MM.

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.

2021 Mar. NPJ Parkinsons Dis.7(1):29.
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