Contrasting effects of peripheral decarboxylase inhibitors on plasma activity of aromatic-L-amino acid decarboxylase and semicarbazide-sensitive amine oxidase in Parkinson's disease

Abstract

The peripheral decarboxylase inhibitors benserazide and carbidopa, often administered in combination with L-dopa in the treatment of Parkinson's disease, are also very good inhibitors of semicarbazide-sensitive amine oxidase (SSAO). In untreated patients and in patients treated with L-dopa alone, plasma SSAO activity is normal. In patients treated with L-dopa plus benserazide or carbidopa (Madopar ® or Sinemet ®), however, plasma SSAO activity is strongly inhibited, contrary to the paradoxical 3-fold increase in plasma aromatic-L-amino acid decarboxylase activity we reported previously. Single-dose and longitudinal studies show that the SSAO inhibition proceeds rapidly and increases even further to nearly complete inhibition after continued treatment, while aromatic-L-amino acid decarboxylase activity only transiently decreases after a single dose and increases slowly with continued treatment above pretreatment levels. Dialysis experiments confirm that the binding of benserazide to SSAO is irreversible, especially after chronic treatment. The lack of knowledge about the exact function of SSAO precludes definite conclusions about the effect of this chronic SSAO inhibition on patients. Careful follow-up studies of patients treated with Madopar ® or Sinemet ® might provide further information about the possible physiological role of SSAO.