Presence of N-methyl-norsalsolinol in the CSF: correlations with dopamine metabolites of patients with Parkinson's disease

Abstract

We could identify the MPTP-like compound and isoquinoline derivative N-methyl-norsalsolinol (2-MDTIQ) in cerebrospinal fluid (CSF) of patients with Parkinson's disease. The presence of 2-MDTIQ negatively correlated with the disease duration. In order to study the relationship between presence of 2-MDTIQ and dopamine metabolism, we examined 3-O-methyl-dopa (MDOPA) and homovanillic acid (HVA) levels in CSF of 15 normal control subjects and 34 patients with Parkinson's disease (PD). In the PD group in which 2-MDTIQ was detected, the HVA/MDOPA ratio was also negatively correlated with the duration of the disease and was increased when compared to patients without 2-MDTIQ. Since in both PD groups the daily L-dopa dose, the mean MDOPA levels, and the daily L-dopa dose/MDOPA ratio were nearly identical the results are not related to different L-dopa medications. In vitro experiments demonstrated 2-MDTIQ to inhibit monoamine oxidase activity in the caudate-putamen. These results suggest that 2-MDTIQ indicates an increased dopamine turnover in patients with PD. The enhanced metabolism at the beginning of the disease is not due to the presence of 2-MDTIQ since it inhibits dopamine metabolism. Thus, 2-MDTIQ, probably endogenously synthesized from dopamine, appears as a result of a compensatively activated dopaminergic system.