L-dihydroxyphenylalanine and its decarboxylase: new ideas on their neuroregulatory roles

Recent experimental reports concerning L-dihydroxyphenylalanine (L-DOPA) and aromatic L-amino acid decarboxylase (AADC, L-DOPA decarboxylase) are reviewed in this article. Both in vitro and in vivo data now suggest that L-DOPA is an endogenous neuroactive compound that is released from neurons and acts as a neurotransmitter or neuromodulator in the brain. Administration of exogenous L-DOPA affects dopamine receptor status, AADC activity, and mitochondrial oxidation in experimental animals. The type and severity of these effects depend on the duration of the treatment. These findings may partly explain the limited efficacy of L-DOPA therapy in Parkinson's disease (PD). AADC also plays a controlling role in the central nervous system, being a regulatory enzyme in the synthesis of a putative neuromodulator 2-phenylethylamine and other trace amines. Recent experimental findings on AADC activity and localisation are of importance because they suggest that striatal [18F]DOPA uptake used as an indicator of PD progression in positron emission tomography (PET) studies is likely to overestimate nigrostriatal integrity in advanced PD. Possible new PET tracers of presynaptic dopaminergic function are discussed in this context.