[The effect of droxidopa on the monoamine metabolsim in the human brain].
Droxidopa (L-threo-3,4-dihydroxyphenylserine) is an artificial amino acid, which is used to supplement noradrenaline (NA) in neurodegenerative disorders. Droxidopa is decarboxylated into NA by aromatic L-amino acid decarboxylase in the brain, but its effects on other monoamine neurotransmitters, such as dopamine (DA) and serotonin (5-HT) have not been systematically examined. The monoamine metabolism has been suggested to interact with each other in the brain, and by analysis of the cerebrospinal fluid, L-DOPA, a precursor amino acid used for supplement of DA, was found to inhibit serotonin synthesis in the brain. To examine the effects of droxidopa on the monoamine metabolism, the intraventricular fluid of the patients administered with droxidopa and L-DOPA was analyzed. The levels of monoamines, their precursor amino acids, and their metabolites were compared between the patients administered with L-DOPA. In the patients administered by droxidopa and L-DOPA, droxidopa was shown to increase the concentrations of monoamines (NA, DA and 5-HT), but the difference was not statistically significant by comparison with those treated by L-DOPA alone. The metbolites of DA and 5-HT by monoamine oxidase, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA) were also found to increase by droxidopa administration. On the other hand, the metabolites of NA and DA by catechol-O-methyltransferase (COMT), normetanephrine (NMN) and 3-methoxytyramine (3-MT), decreased in the patients treated with droxidopa and L-DOPA compared with the patients administered with L-DOPA alone and control patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Maruyama
W
W
Department of Neurology, Nagoya University School of Medicine.
Naoi
M
M
Narabayashi
H
H
D000328:Adult; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D015103:Droxidopa / Q000008:administration & dosage / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007980:Levodopa / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism
D015306:Biogenic Monoamines; D007980:Levodopa; D015103:Droxidopa