The mechanism of perturbation in monoamine metabolism by L-dopa therapy: in vivo and in vitro studies.
J Neural Transm Gen Sect
; 90(3): 183-97, 1992.
Article
em En
| MEDLINE
| ID: mdl-1363050
ABSTRACT
In the cerebrospinal fluid of the patients with Parkinson's disease treated with L-DOPA, L-3-O-methyldopa was the major metabolite of administered L-DOPA. Using a dopaminergic cell model, clonal rat phenochromocytoma PC 12h cells, and by microdialysis of the rat striatum it was proved that L-3-O-methyldopa was taken up into monoamine neurons by transport system specific for aromatic L-amino acids and inhibited transport of L-DOPA and other amino acids competitively. L-3-O-Methyldopa depleted allosteric regulation of the biopterin cofactor on activity of tyrosine hydroxylase, the rate-limiting enzyme of catecholamine synthesis. Depletion of the allostery may perturb the buffer action of endogenous L-DOPA synthesis that stabilizes dopamine level in the brain. By these mechanisms L-3-O-methyldopa may reduce clinical effectiveness of administered L-DOPA and be involved in wearing-off phenomenon. L-DOPA inhibited the activity of tryptophan hydroxylase and thus serotonin synthesis, which may be related to psychiatric side-effects in the patients under L-DOPA therapy.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Monoaminas Biogênicas
/
Levodopa
Limite:
Aged
/
Animals
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
J Neural Transm Gen Sect
Ano de publicação:
1992
Tipo de documento:
Article
País de afiliação:
Japão