Bachus_1999_Pharmacogenet_9_661

Reference

Title : The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6 - Bachus_1999_Pharmacogenet_9_661
Author(s) : Bachus R , Bickel U , Thomsen T , Roots I , Kewitz H
Ref : Pharmacogenetics , 9 :661 , 1999
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. Two novel metabolites of galanthamine have been isolated from the urine 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 Vmax 5.2 nmol/mg protein/h and Km 187 microM. Ki of quinidine to inhibit O-demethylation was 28 nM. To inhibit cholinesterases, O-demethylgalanthamine was 10-fold more selective for acetylcholinesterase (AChE) versus butyrylcholinesterase (BCHE) than galanthamine. After glucuronidation, O-demethylgalanthamine failed to inhibit AChE and BCHE. N-Demethylgalanthamine inhibited cholinesterases less potently than galanthamine.
ESTHER : Bachus_1999_Pharmacogenet_9_661
PubMedSearch : Bachus_1999_Pharmacogenet_9_661
PubMedID: 10634129

Related information

Inhibitor Galanthamine

Citations formats

Bachus R, Bickel U, Thomsen T, Roots I, Kewitz H (1999)
The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6
Pharmacogenetics 9 :661

Bachus R, Bickel U, Thomsen T, Roots I, Kewitz H (1999)
Pharmacogenetics 9 :661

Array
(
    [id] => 49621
    [paper] => Bachus_1999_Pharmacogenet_9_661
    [author] => Bachus R || Bickel U || Thomsen T || Roots I || Kewitz H
    [year] => 1999
    [title] => The O-demethylation of the antidementia drug galanthamine is catalysed by cytochrome P450 2D6
    [journal] => Pharmacogenetics
    [volume] => 9
    [page] => 661
    [medline] => 10634129
    [abstract] => Bachus_1999_Pharmacogenet_9_661
    [kin_reference] => 
    [mutation] => 
    [kinetic_parameter] => 
    [inhibitor] => Galanthamine
    [kin_value] => 
    [substrate] => 
    [gene_locus] => Array
        (
        )

    [family] => 
    [interact_gene_locus] => 
    [xenobiotic_sensitivity] => 
    [news] => 
    [likid_reference] => 
    [lip_reference] => 
    [gene_locus_frgt] => 
    [structure] => 
    [comment] => 
    [chemical] => 
    [arpigny_jaeger] => 
    [reactivator] => 
    [disease] => 
    [enzyme] => 
    [risk_factor] => 
    [tissue] => 
    [sub_tissue] => 
    [activity] => 
    [specific_activity] => 
    [disease_by_interaction] => 
    [abstract_text] => Array
        (
            [id] => 10459
            [longtext] => Bachus_1999_Pharmacogenet_9_661
            [content] => 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. Two novel metabolites of galanthamine have been isolated from the urine 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 Vmax 5.2 nmol/mg protein/h and Km 187 microM. Ki of quinidine to inhibit O-demethylation was 28 nM. To inhibit cholinesterases, O-demethylgalanthamine was 10-fold more selective for acetylcholinesterase (AChE) versus butyrylcholinesterase (BCHE) than galanthamine. After glucuronidation, O-demethylgalanthamine failed to inhibit AChE and BCHE. N-Demethylgalanthamine inhibited cholinesterases less potently than galanthamine.
        )

)