Stereospecific occurrence of a parkinsonism-inducing catechol isoquinoline, N-methyl(R)salsolinol, in the human intraventricular fluid.
N-Methyl(R)salsolinol, an endogenous neurotoxin, has been proposed to be closely involved in the pathogenesis of Parkinson's disease. The selective toxicity to dopaminergic neurons was strictly limited for (R)-enantiomer of N-methylsalsolinol. Its precursor, (R)salsolinol was enzymatically synthesized from dopamine and acetaldehyde in human. However, it has never been examined whether a non-enzymatic reaction produces racemic salsolinol derivatives from dopamine especially in patients under L-DOPA therapy. To clarify the point, their contents were examined in intraventricular fluid from parkinsonian patients administrated with L-DOPA. Only (R)-enantiomer of N-methylsalsolinol and very low concentration of salsolinol could be detected. The results suggest that N-methyl(R)salsolinol synthesis may not depend on dopamine level, but on the activity of enzymes related to its synthesis and/or catabolism. The results are discussed in relation to pathogenesis Parkinson's disease.
Maruyama
W
W
Department of Neurology, Nagoya University School of Medicine, Japan.
Narabayashi
H
H
Dostert
P
P
Naoi
M
M
D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D001826:Body Fluids / Q000737:chemistry*; D002552:Cerebral Ventricles / Q000737:chemistry*; D005260:Female; D006801:Humans; D007546:Isoquinolines / Q000032:analysis*; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D015394:Molecular Structure; D009498:Neurotoxins / Q000032:analysis*; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D013237:Stereoisomerism
D000978:Antiparkinson Agents; D007546:Isoquinolines; D009498:Neurotoxins; D007980:Levodopa; C036617:salsolinol