Increased systemic levels of norsalsolinol derivatives are induced by levodopa treatment and do not represent biological markers of Parkinson's disease

Endogenously synthesised norsalsolinol derivatives are elevated in Parkinson's disease (PD) and have been considered potentially useful biological markers of the disease. However, little is known about the impact of dopaminergic drugs on the formation of these compounds. We prospectively examined the urine concentrations of norsalsolinol, N-methyl-norsalsolinol and salsolinol in 47 PD patients and 14 control subjects. Patients and control subjects were re-examined after approximately 1 year to assess long term changes. Norsalsolinol derivatives were low in controls and untreated patients with early PD. Increased urine concentrations of norsalsolinol derivatives were significantly associated with levodopa treatment. They were elevated more markedly in the urine of patients treated with high (>600 mg daily) doses of levodopa compared with patients receiving medium (300-600 mg) or low (<300 mg) doses of the drug. There was no correlation with disease parameters such as the severity of motor disability or deficits in the cognitive performance. In the patient group, the concentrations of all three norsalsolinol derivatives declined over the period of investigation, however, they still remained elevated compared with the control group. We conclude that systemic levels of norsalsolinol derivatives in treated patients with PD are likely to derive from the metabolism of levodopa and cannot be regarded as intrinsic markers of the disease. The limited ability of norsalsolinol derivatives to pass the blood-brain barrier prevents an intracerebral accumulation of these possibly harmful compounds, which are biochemically similar to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.