A dopaminergic neurotoxin, 1(R), 2(N)-dimethyl-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 nigro-striatal system of the human brain.
N-Methyl(R)salsolinol was found to be an endogenous dopaminergic neurotoxin inducing parkinsonism in rodents and to increase in the cerebrospinal fluid of parkinsonian patients. The amounts of N-methyl(R)salsolinol and related compounds in the human brain regions were quantitatively analyzed. Only the (R)-enantiomer of salsolinol derivatives were detected, which suggests their enzymatic synthesis in situ. In the nigro-striatal system, the concentration of N-methyl(+)salsolinol was higher than in the frontal cortex, and its oxidized catechol isoquinolinium ion was detected only in the substantia nigra significantly. The accumulation of these neurotoxins in the nigro-striatal region might account for selective cell death of dopamine neurons in the substantia nigra of Parkinson's disease.
Maruyama
W
W
Department of Basic Gerontology, National Institute for Longevity Sciences, Obu, Japan.
Sobue
G
G
Matsubara
K
K
Hashizume
Y
Y
Dostert
P
P
Naoi
M
M
D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D006801:Humans; D007546:Isoquinolines / Q000378:metabolism*; D009498:Neurotoxins / Q000378:metabolism*; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D012490:Salsoline Alkaloids / Q000378:metabolism*; D013237:Stereoisomerism; D013378:Substantia Nigra / Q000378:metabolism*; D044005:Tetrahydroisoquinolines; D014018:Tissue Distribution
D015259:Dopamine Agents; D007546:Isoquinolines; D009498:Neurotoxins; D012490:Salsoline Alkaloids; D044005:Tetrahydroisoquinolines; C069193:1,2-dimethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline; C032837:salsoline