SCH 23390 enhances exogenous L-DOPA decarboxylation in nigrostriatal neurons

Exogenous L-DOPA enhances dopamine metabolism in the intact and denervated striatum, and is the treatment of choice for Parkinsonism. Aromatic L-amino acid decarboxylase (AAAD) converts L-DOPA to dopamine. Blockade of dopamin e D-1-like receptors increases the activity of AAAD in both intact and dene rvated striatum. A single dose of SCH 23390, a dopamine D-1-like receptor a ntagonist, increases the activity of AAAD in the striatum and midbrain and induces small changes in dopamine metabolism. When L-DOPA is administered a fter SCH 23390, there is a significant increase in the formation of 3,4-dih ydroxyphenylacetic acid and dopamine turnover in striatum and midbrain comp ared to L-DOPA alone? suggesting further enhancement of dopamine metabolism . When the studies are repeated in the MPTP mouse model of Parkinson's dise ase, there is significantly more dopamine metabolism in the striatum of les ioned mice pretreated with SCH 23390 than in a comparison group treated wit h L-DOPA alone. These studies suggest that it may be possible to enhance th e conversion of L-DOPA to dopamine in Parkinson's disease patients by admin istering substances that augment brain AAAD.