Plasma levels of the beta-carbolines harman and norharman in Parkinson's disease.
Several lines of evidence suggest that endogenous and exogenous toxins may play a major role in the pathogenesis of Parkinson's disease (PD). In vivo aromatic beta-carbolines, like harman or norharman, may easily be formed by cyclization of indoleamines with e.g. aldehydes. Because of the structural similarity to MPTP, beta-carbolines have been proposed as endogenous toxins. For further elucidation of the role of beta-carbolines in neurodegenerative disorders, harman and norharman plasma levels were measured in 36 patients with PD and compared to an age- and sex-matched control group. Plasma levels of norharman in PD were significantly higher compared to the control group. Harman in the plasma of Parkinsonian patients was also elevated compared to controls, but this difference was not significant. Correlation of beta-carbolines with plasma levels of L-dopa, oral doses of bromocriptine and selegiline in treated Parkinsonian patients showed no significant results. On the one hand these results may suggest a possible role of beta-carbolines in the pathophysiological processes initiating PD, by, e.g., inducing mitochondrial respiratory inhibition like MPP+. One may speculate, however, that elevated levels of norharman and harman are due to an endogenous upregulation caused by unknown metabolic processes.
Kuhn
W
W
Department of Neurology, Ruhr University of Bochum, Germany.
Müller
T
T
Grosse
H
H
Dierks
T
T
Rommelspacher
H
H
D000368:Aged; D000978:Antiparkinson Agents / Q000097:blood / Q000627:therapeutic use; D001971:Bromocriptine / Q000008:administration & dosage / Q000627:therapeutic use; D002243:Carbolines / Q000097:blood*; D005260:Female; D006801:Humans; D007980:Levodopa / Q000097:blood / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D008928:Mitochondria; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy; D012642:Selegiline / Q000008:administration & dosage / Q000627:therapeutic use
D000978:Antiparkinson Agents; D002243:Carbolines; D012642:Selegiline; D001971:Bromocriptine; D007980:Levodopa