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Titolo:
The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6
Autore:
Bachus, R; Bickel, U; Thomsen, T; Roots, I; Kewitz, H;
Indirizzi:
Humboldt Univ, Univ Clin Charite, Dept Psychiat, D-10098 Berlin, Germany Humboldt Univ Berlin Germany D-10098 t Psychiat, D-10098 Berlin, Germany Univ Marburg, Inst Physiol, Marburg, Germany Univ Marburg Marburg Germany iv Marburg, Inst Physiol, Marburg, Germany Pharm Plan Net Contract Res, Monchengladbach, Germany Pharm Plan Net Contract Res Monchengladbach Germany engladbach, Germany Humboldt Univ, Univ Clin Charite, Inst Clin Pharmacol, Berlin, Germany Humboldt Univ Berlin Germany rite, Inst Clin Pharmacol, Berlin, Germany Free Univ Berlin, Univ Clin Benjamin Franklin, Inst Clin Pharmacol, D-1000Berlin, Germany Free Univ Berlin Berlin Germany D-1000 Pharmacol, D-1000Berlin, Germany
Titolo Testata:
PHARMACOGENETICS
fascicolo: 6, volume: 9, anno: 1999,
pagine: 661 - 668
SICI:
0960-314X(199912)9:6<661:TOOTAD>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
SPARTEINE OXIDATION; HUMAN-LIVER; DEBRISOQUINE HYDROXYLATION; EXTENSIVE METABOLIZERS; QUINIDINE TREATMENT; ALZHEIMERS-DISEASE; INHIBITION; CODEINE; PHARMACOKINETICS; INVIVO;
Keywords:
galanthamine; metabolism; cytochrome P450 2D6;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
41
Recensione:
Indirizzi per estratti:
Indirizzo: Bachus, R Humboldt Univ, Univ Clin Charite, Dept Psychiat, Schumannstr 20-21, D-10098 Berlin, Germany Humboldt Univ Schumannstr 20-21 Berlin GermanyD-10098 Germany
Citazione:
R. Bachus et al., "The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6", PHARMACOGEN, 9(6), 1999, pp. 661-668

Abstract

Galanthamine proved effective in symptomatic treatment of senile dementia of Alzheimer's type. The aim of this study was to elucidate the metabolism of galanthamine, True novel metabolites of galanthamine have been isolated from the mine of eight young men after single doses of 10-15 mg. Some 19.8%of the doses were excreted as O-demethylgalanthamine glucuronide, 5% as N-demethylgalanthamine, 25.1% as galanthamine, and 0.8% as epigalanthamine, After coadministration of quinidine hydrogen sulfate, which inhibits cytochrome P450 2D6 (CYP2D6) selectively, O-demethylgalanthamine glucuronide was highly diminished in urine. In vitro, human liver microsomes metabolized galanthamine to O-demethylgalanthamine with V-max 5.2 nmol/mg protein/h and K-m 187 mu M. K-i of quinidine to inhibit O-demethylation was 28 nM. To inhibit cholinesterases, O-demethylgalanthamine was 10-fold more selective for acetylcholinesterase (AChE) versus butyrylcholinesterase (BuChE) than galanthamine, After glucuronidation, O-demethylgalanthamine failed to inhibit AChE and BuChE, N-Demethylgalanthamine inhibited cholinesterases less potentlythan galanthamine. Pharmacogenetics 9:661-668 (C) 1999 Lippincott Williams& Wilkins.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/01/20 alle ore 18:33:15