The metabolism of L-DOPA and L-threo-3,4-dihydroxyphenylserine and their effects on monoamines in the human brain: analysis of the intraventricular fluid from parkinsonian patients.
The monoamines and their metabolites were analyzed in the intraventricular fluid of parkinsonian patients treated with L-DOPA alone or together with L-threo-3,4-dihydroxyphenylserine (L-threo-DOPS), the precursor amino acids of dopamine and noradrenaline, respectively. In the intraventricular fluid of the patients administered with L-DOPA, the level of dopamine metabolites were higher than control, suggesting enhanced turnover of dopamine in the brain. However, L-DOPA administration increased free noradrenaline only slightly, and did not affect serotonin and its metabolite. On the other hand, by administration of L-DOPA combined with L-threo-DOPS, the levels of monoamines increased in general, whereas the monoamine metabolites by catechol-O-methyltransferase were reduced compared with those in the patients treated with L-DOPA alone. Only a minor part of L-threo-DOPS was metabolized into noradrenaline by aromatic L-amino acid decarboxylase, and it was metabolized mainly by two other enzymes, catechol-O-methyltransferase and DOPS-aldolase in the brain. An overview of the metabolism of neurotransmitters in the brain proved to be useful to evaluate the therapeutic effects of these precursor amino acids.
Maruyama
W
W
Department of Neurology, Nagoya University School of Medicine, Japan.
Naoi
M
M
Narabayashi
H
H
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000328:Adult; D000978:Antiparkinson Agents / Q000378:metabolism* / Q000627:therapeutic use; D015306:Biogenic Monoamines / Q000378:metabolism*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000378:metabolism*; D003131:Combined Modality Therapy; D004298:Dopamine / Q000378:metabolism; D015103:Droxidopa / Q000378:metabolism* / Q000627:therapeutic use*; D005260:Female; D006719:Homovanillic Acid / Q000378:metabolism; D006801:Humans; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007980:Levodopa / Q000378:metabolism* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D012016:Reference Values; D013238:Stereotaxic Techniques; D013788:Thalamus / Q000601:surgery
D000978:Antiparkinson Agents; D015306:Biogenic Monoamines; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D006897:Hydroxyindoleacetic Acid; D015103:Droxidopa; D004298:Dopamine; D009638:Norepinephrine; D006719:Homovanillic Acid