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 patient s with Parkinson's disease. The presence of 2-MDTIQ negatively correla ted with the disease duration. In order to study the relationship betw een presence of 2-MDTIQ and dopamine metabolism, we examined 3-O-methy l-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 increas ed 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 dos e/MDOPA ratio were nearly identical the results are not related to dif ferent L-dopa medications. In vitro experiments demonstrated ZMDTIQ to inhibit monoamine oxidase activity in the caudate-putamen. These resu lts suggest that 2-MDTIQ indicates an increased dopamine turnover in p atients with PD. The enhanced metabolism at the beginning of the disea se is not due to the presence of ZMDTIQ since it inhibits dopamine met abolism. Thus, 2-MDTIQ, probably endogenously synthesized from dopamin e, appears as a result of a compensatively activated dopaminergic syst em.