PRESENCE OF N-METHYL-NORSALSOLINOL IN THE CSF - CORRELATIONS WITH DOPAMINE METABOLITES OF PATIENTS WITH PARKINSONS-DISEASE

We could identify the MPTP-like compound and isoquinoline derivative N-methyl-norsalsolinol (ZMDTIQ) 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 ZMDTIQ 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 ZMDTIQ since it inhibits dopamine metabolism. Thus, 2-MDTIQ, probably endogenously synthesized from dopamine, appears as a result of a compensatively activated dopaminergic system.