A DOPAMINERGIC NEUROTOXIN, THYL-6,7-DIHYDROXY-1,2,3,4-TETRAHYDROISOQUINOLINE, N-METHYL(R)SALSOLINOL, AND ITS OXIDATION-PRODUCT, 1,2(N)-DIMETHYL-6,7-DIHYDROXYISOQUINOLINIUM ION, ACCUMULATE IN THE NIGROSTRIATAL SYSTEM OF THE HUMAN BRAIN

N-Methyl(R)salsolinol was found to be an endogenous dopaminergic neuro toxin inducing parkinsonism in rodents and to increase in the cerebros pinal fluid of parkinsonian patients. The amounts of N-methyl(R)salsol inol and related compounds in the human brain regions were quantitativ ely analyzed. Only the (R)-enantiomer of salsolinol derivatives were d etected, which suggests their enzymatic synthesis in situ. In the nigr o-striatal system, the concentration of N-methyl(R)salsolinol was high er than in the frontal cortex, and its oxidized catechol isoquinoliniu m ion was detected only in the substantia nigra significantly. The acc umulation of these neurotoxins in the nigro-striatal region might acco unt for selective cell death of dopamine neurons in the substantia nig ra of Parkinson's disease. (C) 1997 Elsevier Science Ireland Ltd.