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Titolo:
BIA 3-202, a novel catechol-O-methyltransferase inhibitor, enhances the availability of L-DOPA to the brain and reduces its O-methylation
Autore:
Parada, A; Loureiro, AI; Vieira-Coelho, MA; Hainzl, D; Soares-Da-Silva, P;
Indirizzi:
BIAL, Dept Res & Dev, P-4785 S Mamede Do Coronado, Portugal BIAL S MamedeDo Coronado Portugal P-4785 S Mamede Do Coronado, Portugal Fac Med Porto, Dept Pharmacol & Therapeut, P-4200 Oporto, Portugal Fac MedPorto Oporto Portugal P-4200 Therapeut, P-4200 Oporto, Portugal
Titolo Testata:
EUROPEAN JOURNAL OF PHARMACOLOGY
fascicolo: 1, volume: 420, anno: 2001,
pagine: 27 - 32
SICI:
0014-2999(20010518)420:1<27:B3ANCI>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
SELECTIVE COMT INHIBITORS; PARKINSONS-DISEASE; TOLCAPONE; METABOLISM; LEVODOPA; PHARMACOKINETICS; ENTACAPONE; ADJUNCTS; RAT;
Keywords:
L-3,4-dihydroxyphenylalanine (L-DOPA); 3-O-methyl-3,4-dihydroxyphenylalanine (3-O-methyl-L-DOPA); brain; BIA 3-202;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Soares-Da-Silva, P BIAL, Dept Res & Dev, P-4785 S Mamede Do Coronado, Portugal BIAL S Mamede Do Coronado Portugal P-4785 o, Portugal
Citazione:
A. Parada et al., "BIA 3-202, a novel catechol-O-methyltransferase inhibitor, enhances the availability of L-DOPA to the brain and reduces its O-methylation", EUR J PHARM, 420(1), 2001, pp. 27-32

Abstract

1-[3,4-Dihydroxy-5-nitrophenyl]-2-phenyl (BIA 3-202) is a new long-acting catechol-O-methyltransferase (COMT) inhibitor with Limited access to the brain. The present study evaluated the interference of BIA 3-202 upon levels of L-3,4-dihydroxyphenylalanine (L-DOPA) and metabolites in plasma (3-O-methyl-L-DOPA) and brain [3-O-methyl-L-DOPA, dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA)] in rats orally treated with L-DOPA (20 mg/kg) plus benserazide (30 mg/kg). At different time points (1, 3and 6 h) after the administration of BIA 3-202 (0, 3, 10 and 30 mg/kg) or L-DOPA plus benserazide, rats were sacrificed and the right striatum was quickly dissected out and stored for the assay of L-DOPA, 3-O-methyl-L-DOPA, dopamine and amine metabolites. Levels of L-DOPA, 3-O-methyl-L-DOPA, dopamine, DOPAC and HVA in the striatum in L-DOPA plus benserazide-treated rats were higher than in vehicle-treated rats. However, this increase in striatalL-DOPA, dopamine, DOPAC and HVA was, in a dose- and time-dependent manner,even higher (P < 0.05) in rats given BIA 3-202 (3, 10 and 30 mg/kg). This effect was accompanied by a marked decrease in 3-O-methyl-L-DOPA levels in the striatum of L-DOPA plus benserazide-treated rats. Increases in levels of L-DOPA and decreases in 3-O-methyl-L-DOPA levels in plasma also accompanied the administration of BIA 3-202. BIA 3-202 did not significantly affect levels of DOPAC and HVA in the striatum in vehicle-treated rats. It is concluded that administration of BIA 3-202 enhances the availability of L-DOPA.to the brain by reducing its O-methylation in the periphery, which may prove beneficial in parkinsonian patients treated with L-DOPA plus an aromaticamino acid decarboxylase inhibitor. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/07/20 alle ore 13:27:33